Pub Date : 2023-07-07DOI: 10.46235/1028-7221-1533-ctc
MariIa K. Serebriakova, A. Ilves, V. M. Lebedev, O. M. Novoselova, L. Prakhova, I. Kudryavtsev
Using multicolor flow cytometry, the main cytotoxic T lymphocytes (Tcyt) subsets were identified, based on the expression of CD45RA and CD62L in paired samples of peripheral blood and cerebrospinal fluid from the patients during the relapse (n = 32) and remission (n = 20) of multiple sclerosis (MS), as well as in the peripheral blood samples of healthy volunteers (n = 51). During the relapse of MS, we have observed a decreased relative number of CD3+CD4+ cells and CD4/CD8 ratio in cerebrospinal liquor. In peripheral blood taken from the relapsed MS patients, we have found significant correlations between EDSS score and absolute counts (r = -0,430, p = 0.014), and with relative numbers of CD45RA+CD62L+Tcyt (r = -0,502, p = 0.003). In remission state of MS, the relative numbers of blood CD45RA-CD62L-Tcyt cells exhibited a significant decrease (p = 0.005) to 8.70% (6.51-11.63) against control group with 12.18% (10.38-15.24), although it did not significantly differ (p = 0.114) from the relapsed patients with 11.31% (8.28-13.90). Studies of liquor samples have shown that, during MS relapse, the percentage of CD45RA-CD62L-Tcyt was increased (p = 0.027) up to 8.16% (6.40-11.40), while in remission state these cells comprised only 6.49% (4.51-8.39) from the total CD3+ cell number. During relapse of MS, some positive correlations were revealed between the relative number of nave, CM, EM and TEMRA Tcyt from liquor, and the percentages, as well as contents of similar T cell subsets in peripheral blood samples. The inverse relationship between the level of EM Tcyt from liquor and peripheral blood naive cells showed the close relationship between these two Tcyt subsets and clinical manifestations of MS (i.e., scores of EDSS scale). During the remission period, most of these correlations are disrupted. Further investigations of cytotoxic T cells dynamics in peripheral blood and cerebrospinal fluid will help to approach the understanding of MS pathogenesis by revealing novel markers for the clinical prognosis in this disorder.
{"title":"Cytotoxic T cell subsets in peripheral blood and cerebrospinal fluid from patients with multiple sclerosis","authors":"MariIa K. Serebriakova, A. Ilves, V. M. Lebedev, O. M. Novoselova, L. Prakhova, I. Kudryavtsev","doi":"10.46235/1028-7221-1533-ctc","DOIUrl":"https://doi.org/10.46235/1028-7221-1533-ctc","url":null,"abstract":"Using multicolor flow cytometry, the main cytotoxic T lymphocytes (Tcyt) subsets were identified, based on the expression of CD45RA and CD62L in paired samples of peripheral blood and cerebrospinal fluid from the patients during the relapse (n = 32) and remission (n = 20) of multiple sclerosis (MS), as well as in the peripheral blood samples of healthy volunteers (n = 51). During the relapse of MS, we have observed a decreased relative number of CD3+CD4+ cells and CD4/CD8 ratio in cerebrospinal liquor. In peripheral blood taken from the relapsed MS patients, we have found significant correlations between EDSS score and absolute counts (r = -0,430, p = 0.014), and with relative numbers of CD45RA+CD62L+Tcyt (r = -0,502, p = 0.003). In remission state of MS, the relative numbers of blood CD45RA-CD62L-Tcyt cells exhibited a significant decrease (p = 0.005) to 8.70% (6.51-11.63) against control group with 12.18% (10.38-15.24), although it did not significantly differ (p = 0.114) from the relapsed patients with 11.31% (8.28-13.90). Studies of liquor samples have shown that, during MS relapse, the percentage of CD45RA-CD62L-Tcyt was increased (p = 0.027) up to 8.16% (6.40-11.40), while in remission state these cells comprised only 6.49% (4.51-8.39) from the total CD3+ cell number. During relapse of MS, some positive correlations were revealed between the relative number of nave, CM, EM and TEMRA Tcyt from liquor, and the percentages, as well as contents of similar T cell subsets in peripheral blood samples. The inverse relationship between the level of EM Tcyt from liquor and peripheral blood naive cells showed the close relationship between these two Tcyt subsets and clinical manifestations of MS (i.e., scores of EDSS scale). During the remission period, most of these correlations are disrupted. Further investigations of cytotoxic T cells dynamics in peripheral blood and cerebrospinal fluid will help to approach the understanding of MS pathogenesis by revealing novel markers for the clinical prognosis in this disorder.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82322057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-7127-ros
N. V. Mikryukova, N. Kalinina
Chronic urticaria (CU) is a serious issue in clinical allergology. Exact pathogenesis of diseases is unknown despite a fairly large number of studies. From clinical view, CU manifests as wheals and/or angioedema, lasting for more than 6 weeks. It is classified into spontaneous (without obvious triggers) and induced CU (in cases of evident physical and chemical stimuli). It is quite difficult to reveal its cause. Most often, the patients refer to specific foods as a trigger factor. Stress is the second leading cause of CU after breaking the diet. Mental or emotional stress has been shown to cause degranulation of mast cells (MC) and histamine release. Substance P (SP) is a neurotransmitter, which underlies neuroimmune inflammation, being considered the most informative marker of CU. The purpose of our study was to assess a role of SP in the CU pathogenesis and to determine the relationship of SP with known urticaria triggers and comorbidities. We examined 97 patients with CU and 68 apparently healthy individuals matched by sex and age. The levels of histamine and substance P (SP) were determined in blood serum by enzyme immunoassay. The patients were classified into groups, depending on the history of food and drug intolerance, presence of concomitant autoimmune thyroiditis (AIT), influence of stress as a trigger for CU. When analyzing the average levels of histamine and SP in the group of patients suffering from CU, compared with the control group, no significant correlations were found. We detected an almost 3-fold increase of histamine levels in the patients suffering from AIT (28.25 ng/mL versus 83.61 ng/mL). However, when assessing the level of histamine in patients with CU and with a history of food and drug intolerance, trigger stress and AIT, the average values of the indicator did not show significant differences. Meanwhile, when assessing the SP index in patients with a history of drug, food intolerance, AIT and stress as a trigger for CU, we have found a significant increase in SP in the patients when compared with control group (p 0.05). Our results confirm the neuroimmune inflammation system to be involved in genesis of mast cell activation in CU patients. Further studies are required in order to discern a specific phenotype of stress-induced CU and determine the opportunities for its psychopharmacological correction.
{"title":"Role of substance P in the pathogenesis of chronic urticaria","authors":"N. V. Mikryukova, N. Kalinina","doi":"10.46235/1028-7221-7127-ros","DOIUrl":"https://doi.org/10.46235/1028-7221-7127-ros","url":null,"abstract":"Chronic urticaria (CU) is a serious issue in clinical allergology. Exact pathogenesis of diseases is unknown despite a fairly large number of studies. From clinical view, CU manifests as wheals and/or angioedema, lasting for more than 6 weeks. It is classified into spontaneous (without obvious triggers) and induced CU (in cases of evident physical and chemical stimuli). It is quite difficult to reveal its cause. Most often, the patients refer to specific foods as a trigger factor. Stress is the second leading cause of CU after breaking the diet. Mental or emotional stress has been shown to cause degranulation of mast cells (MC) and histamine release. Substance P (SP) is a neurotransmitter, which underlies neuroimmune inflammation, being considered the most informative marker of CU. The purpose of our study was to assess a role of SP in the CU pathogenesis and to determine the relationship of SP with known urticaria triggers and comorbidities. \u0000We examined 97 patients with CU and 68 apparently healthy individuals matched by sex and age. The levels of histamine and substance P (SP) were determined in blood serum by enzyme immunoassay. The patients were classified into groups, depending on the history of food and drug intolerance, presence of concomitant autoimmune thyroiditis (AIT), influence of stress as a trigger for CU. \u0000When analyzing the average levels of histamine and SP in the group of patients suffering from CU, compared with the control group, no significant correlations were found. We detected an almost 3-fold increase of histamine levels in the patients suffering from AIT (28.25 ng/mL versus 83.61 ng/mL). However, when assessing the level of histamine in patients with CU and with a history of food and drug intolerance, trigger stress and AIT, the average values of the indicator did not show significant differences. Meanwhile, when assessing the SP index in patients with a history of drug, food intolerance, AIT and stress as a trigger for CU, we have found a significant increase in SP in the patients when compared with control group (p 0.05). \u0000Our results confirm the neuroimmune inflammation system to be involved in genesis of mast cell activation in CU patients. Further studies are required in order to discern a specific phenotype of stress-induced CU and determine the opportunities for its psychopharmacological correction.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81709072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-10759-iop
Xinyu Hu, Haoyang Wang
Proteinase Activated Receptors (PARs) are the members of G-protein-coupled receptor family and can be cleaved by certain serine proteases to expose a tethered ligand domain, which binds and activates the receptors to initiate multiple signaling cascades. There is some evidence that certain proteases may regulate target cells by activating PARs. There are many studies, in which PARs play important roles in inflammation. One study indicated that PAR2 inhibition and deletion significantly suppressed the degree of inflammation due to decreased IL-6 and IL-1 levels. Another study also showed that PARs activation could mediate reactive oxygen species production and MAPK signaling leading to alveolar inflammation. In addition, platelet-derived CAPN1 can trigger the vascular inflammation associated with diabetes via cleavage of PAR1 and the release of TNF from the endothelial cell surface, and sarsasapogenin may alleviate diabetic nephropathy by the downregulation of PAR1. Another Phellodendron amurense bark extract can suppress the particulate matter-induced Ca2+ influx caused by direct action upon PAR2, alleviating inflammation and maintaining homeostatic levels of cell adhesion components. There are also other two antagonists of I-287 and GB88, which can reduce the PAR2-mediated inflammatory reaction. In this study, we tested expression of PARs and IL-5, IL-6, RANTES and ECP release from human blood eosinophils using different enzymes and PAR agonists. The expression of PARs was assessed in human blood eosinophils by flow cytometry and RT-PCR, and the levels of cytokine and eosinophil cationic protein (ECP) in the cultured supernatants were determined with ELISA kits. Flow cytometry shows that human eosinophils express PAR2 protein and do not express PAR1, PAR3 and PAR4 proteins. RT-PCR analysis revealed expression of PAR2 and PAR3 genes in human eosinophils. Tryptase, trypsin and elastase can induce significant IL-5, IL-6 and ECP release. Trypsin and elastase may also stimulate RANTES secretion, but tryptase cannot induce the RANTES secretion. Tryptase, trypsin and elastase-induced cytokine and ECP release from human blood eosinophils most likely occurs via activation of PAR2.
{"title":"Involvement of PAR2 in inflammatory mediator release from human blood eosinophils","authors":"Xinyu Hu, Haoyang Wang","doi":"10.46235/1028-7221-10759-iop","DOIUrl":"https://doi.org/10.46235/1028-7221-10759-iop","url":null,"abstract":"Proteinase Activated Receptors (PARs) are the members of G-protein-coupled receptor family and can be cleaved by certain serine proteases to expose a tethered ligand domain, which binds and activates the receptors to initiate multiple signaling cascades. There is some evidence that certain proteases may regulate target cells by activating PARs. There are many studies, in which PARs play important roles in inflammation. One study indicated that PAR2 inhibition and deletion significantly suppressed the degree of inflammation due to decreased IL-6 and IL-1 levels. Another study also showed that PARs activation could mediate reactive oxygen species production and MAPK signaling leading to alveolar inflammation. In addition, platelet-derived CAPN1 can trigger the vascular inflammation associated with diabetes via cleavage of PAR1 and the release of TNF from the endothelial cell surface, and sarsasapogenin may alleviate diabetic nephropathy by the downregulation of PAR1. Another Phellodendron amurense bark extract can suppress the particulate matter-induced Ca2+ influx caused by direct action upon PAR2, alleviating inflammation and maintaining homeostatic levels of cell adhesion components. There are also other two antagonists of I-287 and GB88, which can reduce the PAR2-mediated inflammatory reaction. In this study, we tested expression of PARs and IL-5, IL-6, RANTES and ECP release from human blood eosinophils using different enzymes and PAR agonists. The expression of PARs was assessed in human blood eosinophils by flow cytometry and RT-PCR, and the levels of cytokine and eosinophil cationic protein (ECP) in the cultured supernatants were determined with ELISA kits. Flow cytometry shows that human eosinophils express PAR2 protein and do not express PAR1, PAR3 and PAR4 proteins. RT-PCR analysis revealed expression of PAR2 and PAR3 genes in human eosinophils. Tryptase, trypsin and elastase can induce significant IL-5, IL-6 and ECP release. Trypsin and elastase may also stimulate RANTES secretion, but tryptase cannot induce the RANTES secretion. Tryptase, trypsin and elastase-induced cytokine and ECP release from human blood eosinophils most likely occurs via activation of PAR2.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86308001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-9408-ieo
Michael V. Osikov, Anna A. Ageeva, Margarita S. Boyko, Yuriy I. Ageev
High incidence of thermal trauma (TT), increased risk of infectious and non-infectious short- and long-term complications, and limited effectiveness of the therapeutic approaches are the main pre-requisites for searching and pathogenetic justification of new therapies. E.g., melatonin, an endogenous homeostatic regulator with pleiotropic properties, deserves special attention. The aim of the work was to study the effect of local application (as an original dermal film) and systemic usage of melatonin upon concentrations of circulating TNF and IL-4 in the course of experimental thermal trauma. The rates of wound epithelization were expressed as per cent values. The plasma concentrations of IL-4, TNF were determined with automatic enzyme immunoassay analyzer Personal LAB (Italy). In the series with TT, the rate of wound epithelization increased from the 5th to the 20th day of experiment. When using dermal films with MT in experimental TT on days +5, +10 and +20, an increase in the rate of wound epithelization was registered. Under the conditions of intraperitoneal MT injection in experimental TT, the rate of wound epithelization increased on days +10 and +20. A correlation analysis revealed stronger interrelations observed when applying dermal films with MT in thermal trauma, rather than in series with intraperitoneal usage of MT thus suggesting faster repair processes in the first case, along with diminished area of alterations and decreased amounts of cytokines in serum. In experimental TT, the concentrations of TNF and IL-4 increase in blood serum on days +5, +10 and +20. On days +10 and +20, moderate positive associations were recorded between the rate of wound epithelialization and the concentration of serum cytokines. Upon intraperitoneal use of MT in experimental TT, on days +5, +10 and +20, the rate of epithelization increases, along with decrease of TNF concentration on days +10 and +20. On days +5, +10 and +20, moderate negative associations were recorded between the rate of wound epithelization and the concentration of TNF. Under the conditions of using DP with MT with TT, the rate of wound epithelization increases on days 5, 10 and 20, the concentration of TNF decreases in serum, the concentration of IL-4 decreases on day +10. On days +5, +10 and +20, the negative correlations were recorded between the rate of wound epithelization and serum concentrations of TNF and IL-4. A comparative efficiency analysis of MT-containing dermal films versus intraperitoneal use of MT in experimental thermal trauma revealed a more accelerated epithelization of the wound along with earlier decrease in TNF, a greater number and strength of relationships between the rate of the wound epithelization and concentrations of cytokines in blood serum.
{"title":"Immunoregulatory effects of local and systemic use of melatonin in experimental thermal trauma","authors":"Michael V. Osikov, Anna A. Ageeva, Margarita S. Boyko, Yuriy I. Ageev","doi":"10.46235/1028-7221-9408-ieo","DOIUrl":"https://doi.org/10.46235/1028-7221-9408-ieo","url":null,"abstract":"High incidence of thermal trauma (TT), increased risk of infectious and non-infectious short- and long-term complications, and limited effectiveness of the therapeutic approaches are the main pre-requisites for searching and pathogenetic justification of new therapies. E.g., melatonin, an endogenous homeostatic regulator with pleiotropic properties, deserves special attention. The aim of the work was to study the effect of local application (as an original dermal film) and systemic usage of melatonin upon concentrations of circulating TNF and IL-4 in the course of experimental thermal trauma. \u0000The rates of wound epithelization were expressed as per cent values. The plasma concentrations of IL-4, TNF were determined with automatic enzyme immunoassay analyzer Personal LAB (Italy). \u0000In the series with TT, the rate of wound epithelization increased from the 5th to the 20th day of experiment. When using dermal films with MT in experimental TT on days +5, +10 and +20, an increase in the rate of wound epithelization was registered. Under the conditions of intraperitoneal MT injection in experimental TT, the rate of wound epithelization increased on days +10 and +20. A correlation analysis revealed stronger interrelations observed when applying dermal films with MT in thermal trauma, rather than in series with intraperitoneal usage of MT thus suggesting faster repair processes in the first case, along with diminished area of alterations and decreased amounts of cytokines in serum. \u0000In experimental TT, the concentrations of TNF and IL-4 increase in blood serum on days +5, +10 and +20. On days +10 and +20, moderate positive associations were recorded between the rate of wound epithelialization and the concentration of serum cytokines. Upon intraperitoneal use of MT in experimental TT, on days +5, +10 and +20, the rate of epithelization increases, along with decrease of TNF concentration on days +10 and +20. On days +5, +10 and +20, moderate negative associations were recorded between the rate of wound epithelization and the concentration of TNF. Under the conditions of using DP with MT with TT, the rate of wound epithelization increases on days 5, 10 and 20, the concentration of TNF decreases in serum, the concentration of IL-4 decreases on day +10. On days +5, +10 and +20, the negative correlations were recorded between the rate of wound epithelization and serum concentrations of TNF and IL-4. A comparative efficiency analysis of MT-containing dermal films versus intraperitoneal use of MT in experimental thermal trauma revealed a more accelerated epithelization of the wound along with earlier decrease in TNF, a greater number and strength of relationships between the rate of the wound epithelization and concentrations of cytokines in blood serum.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88952847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-1212-soi
S. Kostarev, T. Sereda
Changes of immune system in adolescents during the 2020-2021 pandemic have not been sufficiently studied. The paper concerns features of flow cytometric indexes among the children of different age groups and their immunoglobulin status. The cohort was classified into 12 categories (3 age subgroups, and 4 categories relative to immunoglobulin status). The aim of this work was to investigate changes in the immunograms among children and adolescents during the COVID pandemic evaluated by means of flow cytometry. The methodology of the present work was based on evaluation of immunograms including biochemical studies and flow cytometric analysis. The results of immunological studies of the patients were classified into three age categories. Laboratory diagnostics of human immune system was performed by means of serological and flow cytometric analyses. A total of 250 samples were analyzed in the course of the study. Primary classification of immunograms was performed by immunoglobulin A, M and G status into four categories as follows: absence of disease (R1); immunoglobulin A, M, G values within the reference ranges and active disease (R2); immunoglobulin A and M beyond the reference ranges and passive disease stage (R3); immunoglobulin G and M status and patient recovery process (R4). Eight parameters of immune cells detectable by flow cytometry were chosen for evaluation: total leukocytes, lymphocytes, T lymphocytes (CD3+), B lymphocytes (CD19+), NK cells (CD16+CD56+), T helper cells (CD3+CD4+), NKT cells, and immunoregulation index (CD4+/CD8+). Quantitative assessment of deviations for these indices from the reference values was performed in three distinct age groups under 18 years of age living in the Perm region of the Russian Federation during the pandemic of 2020-2021. The results showed that, in the R1 category, exceeding of reference values was observed for T cells and B cells in the older and younger groups. For T helper cells and immunoregulation index, the reference thresholds were exceeded in the younger groups. The R2 patients had higher leukocyte levels in the older group along with lower immunoglobulin levels. The immunoregulation index in the younger group was accompanied by higher immunoglobulin levels. T cell levels were decreased in the middle group, along with reduced immunoglobulin levels. B lymphocyte values were elevated in the middle group with decreased immunoglobulin levels. In R3 children, a decrease was observed in the immunoregulation index for the older group, with decreased immunoglobulin levels. In the R4 category, the decreased overall deviation of the main immunogram indexes was revealed.
{"title":"Studies of immune parameters in adolescents over the period of 2020-2021","authors":"S. Kostarev, T. Sereda","doi":"10.46235/1028-7221-1212-soi","DOIUrl":"https://doi.org/10.46235/1028-7221-1212-soi","url":null,"abstract":"Changes of immune system in adolescents during the 2020-2021 pandemic have not been sufficiently studied. The paper concerns features of flow cytometric indexes among the children of different age groups and their immunoglobulin status. The cohort was classified into 12 categories (3 age subgroups, and 4 categories relative to immunoglobulin status). The aim of this work was to investigate changes in the immunograms among children and adolescents during the COVID pandemic evaluated by means of flow cytometry. The methodology of the present work was based on evaluation of immunograms including biochemical studies and flow cytometric analysis. \u0000The results of immunological studies of the patients were classified into three age categories. Laboratory diagnostics of human immune system was performed by means of serological and flow cytometric analyses. A total of 250 samples were analyzed in the course of the study. Primary classification of immunograms was performed by immunoglobulin A, M and G status into four categories as follows: absence of disease (R1); immunoglobulin A, M, G values within the reference ranges and active disease (R2); immunoglobulin A and M beyond the reference ranges and passive disease stage (R3); immunoglobulin G and M status and patient recovery process (R4). Eight parameters of immune cells detectable by flow cytometry were chosen for evaluation: total leukocytes, lymphocytes, T lymphocytes (CD3+), B lymphocytes (CD19+), NK cells (CD16+CD56+), T helper cells (CD3+CD4+), NKT cells, and immunoregulation index (CD4+/CD8+). Quantitative assessment of deviations for these indices from the reference values was performed in three distinct age groups under 18 years of age living in the Perm region of the Russian Federation during the pandemic of 2020-2021. \u0000The results showed that, in the R1 category, exceeding of reference values was observed for T cells and B cells in the older and younger groups. For T helper cells and immunoregulation index, the reference thresholds were exceeded in the younger groups. The R2 patients had higher leukocyte levels in the older group along with lower immunoglobulin levels. The immunoregulation index in the younger group was accompanied by higher immunoglobulin levels. T cell levels were decreased in the middle group, along with reduced immunoglobulin levels. B lymphocyte values were elevated in the middle group with decreased immunoglobulin levels. In R3 children, a decrease was observed in the immunoregulation index for the older group, with decreased immunoglobulin levels. In the R4 category, the decreased overall deviation of the main immunogram indexes was revealed.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90710291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-2067-mbd
N. Asfandiyarova, M. Rubtsova
Our aim was to study association between proliferative activity of peripheral blood lymphocytes after COVID, and developing post-COVID syndrome, and to determine whether the cell immunity dysfunction may be regarded as its marker. The retrospective cohort study involved 242 patients (56 males, 186 females, 18 to 85 years old) who contracted new coronavirus infection. Of them, post-COVID syndrome was diagnosed in 180 cases (duration over 3 months). The patients were classified by severity of clinical course of COVID (i.e., presence of acute respiratory disease and pneumonias), and PHA-induced blast transformation of lymphocytes. Along with PHA-induced response, we studied cyclooxygenase (COG)-producing cells by morphological method. Control group consisted of 200 healthy people without any features of coronavirus infection. All patients were questioned and examined by multidisciplinary medical team, dependent on their complaints. We also registered incidence of comorbidities associated with cellular immune deficiency. The patients with post-COVID syndrome exhibited a decrease of PHA-induced lymphocyte proliferation as compared with control group (significant at p 0.01 in cases of acute respiratory infection, and p 0.05 in patients with pneumonia). Activity of COG-producing cells was similar in all groups, independently on presence of post-COVID syndrome. Classification of patients by presence of cellular immune dysfunction (PHA-induced blast transformation 50%) allowed to detect higher activity of COG-producing cells. This enzyme is known to participate in development of inflammation promoting immune deficiency, thus, probably, manifesting in clinical activation of herpesvirus infection following COVID-19. Activity of COG-synthesizing cells was found to be higher in post-COVID syndrome which evolves after middle-severe and severe forms of new coronavirus infection complicated by pneumonias. Chronic inflammation in post-COVID syndrome associated with high activity of COG-producing cells may promote dysfunction of cell immunity, thus being a cause of evolving syndrome, like as its biomarker. Absence of the immune cell dysfunction markers among other post-COVID features leads to decreased registration of post-COVID patients and misinterpretation of the results obtained.
{"title":"May be dysfunction of cellular immunity considered a sign of post-COVID syndrome?","authors":"N. Asfandiyarova, M. Rubtsova","doi":"10.46235/1028-7221-2067-mbd","DOIUrl":"https://doi.org/10.46235/1028-7221-2067-mbd","url":null,"abstract":"Our aim was to study association between proliferative activity of peripheral blood lymphocytes after COVID, and developing post-COVID syndrome, and to determine whether the cell immunity dysfunction may be regarded as its marker. \u0000The retrospective cohort study involved 242 patients (56 males, 186 females, 18 to 85 years old) who contracted new coronavirus infection. Of them, post-COVID syndrome was diagnosed in 180 cases (duration over 3 months). The patients were classified by severity of clinical course of COVID (i.e., presence of acute respiratory disease and pneumonias), and PHA-induced blast transformation of lymphocytes. Along with PHA-induced response, we studied cyclooxygenase (COG)-producing cells by morphological method. Control group consisted of 200 healthy people without any features of coronavirus infection. All patients were questioned and examined by multidisciplinary medical team, dependent on their complaints. We also registered incidence of comorbidities associated with cellular immune deficiency. \u0000The patients with post-COVID syndrome exhibited a decrease of PHA-induced lymphocyte proliferation as compared with control group (significant at p 0.01 in cases of acute respiratory infection, and p 0.05 in patients with pneumonia). Activity of COG-producing cells was similar in all groups, independently on presence of post-COVID syndrome. Classification of patients by presence of cellular immune dysfunction (PHA-induced blast transformation 50%) allowed to detect higher activity of COG-producing cells. This enzyme is known to participate in development of inflammation promoting immune deficiency, thus, probably, manifesting in clinical activation of herpesvirus infection following COVID-19. Activity of COG-synthesizing cells was found to be higher in post-COVID syndrome which evolves after middle-severe and severe forms of new coronavirus infection complicated by pneumonias. \u0000Chronic inflammation in post-COVID syndrome associated with high activity of COG-producing cells may promote dysfunction of cell immunity, thus being a cause of evolving syndrome, like as its biomarker. Absence of the immune cell dysfunction markers among other post-COVID features leads to decreased registration of post-COVID patients and misinterpretation of the results obtained.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76675780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-12045-dot
R. Vasiliev, S. Vasilieva
An important task of industrial animal husbandry is to maintain the reproductive health of female animals. Indolent diseases of the reproductive system remain a big problem. Little information is available on the immunopathogenesis of genital mycoplasmosis. Antibiotic treatment with drugs from tetracycline, macrolide or fluoroquinolone groups is the main approach to treatment of mycoplasmosis. The aim of the present work was to study the dynamics of immunoglobulin contents in blood serum and vaginal secretions of cows with genital mycoplasmosis during therapy with tulathromycin, a semi-synthetic macrolide antibiotic drug. We studied two groups of cows at their interlactation period (n = 8), aged 3-4 years. Control group consisted of clinically healthy cows. The cows from experimental group had confirmed genital mycoplasmosis. They were treated with Traxovet 100 antibiotic (tulathromycin) at a dose of 2.5 mg per 1 kg of animal body weight, by subcutaneous route, 40 days before the expected delivery. Blood serum and vaginal secretions were collected in both groups of animals. The contents of IgG, IgM, IgA immunoglobulins, and sIgA in the vaginal secretion were determined by radial immunodiffusion (Mancini technique). On the 14th day of the experiment, a significant increase in the IgG contents and decreased levels of IgM and IgA were observed in the blood of the cows from experimental group. However, these indexes still remained lower than in healthy cows. In vaginal secretions, a significant decrease in the IgM and sIgA amounts was detected. The immunoglobulin levels in vaginal secretions after antibiotic therapy did not differ from the healthy cows. The use of tulathromycin for treatment of genital mycoplasmosis in pregnant cows shows high therapeutic efficacy, but does not lead to a complete normalization of their immunoglobulin status.
{"title":"Dynamics of the content of immunoglobulins in the blood serum and vaginal secretion of cows with genital mycoplasmosis during treatment with tulathromycin","authors":"R. Vasiliev, S. Vasilieva","doi":"10.46235/1028-7221-12045-dot","DOIUrl":"https://doi.org/10.46235/1028-7221-12045-dot","url":null,"abstract":"An important task of industrial animal husbandry is to maintain the reproductive health of female animals. Indolent diseases of the reproductive system remain a big problem. Little information is available on the immunopathogenesis of genital mycoplasmosis. Antibiotic treatment with drugs from tetracycline, macrolide or fluoroquinolone groups is the main approach to treatment of mycoplasmosis. The aim of the present work was to study the dynamics of immunoglobulin contents in blood serum and vaginal secretions of cows with genital mycoplasmosis during therapy with tulathromycin, a semi-synthetic macrolide antibiotic drug. \u0000We studied two groups of cows at their interlactation period (n = 8), aged 3-4 years. Control group consisted of clinically healthy cows. The cows from experimental group had confirmed genital mycoplasmosis. They were treated with Traxovet 100 antibiotic (tulathromycin) at a dose of 2.5 mg per 1 kg of animal body weight, by subcutaneous route, 40 days before the expected delivery. Blood serum and vaginal secretions were collected in both groups of animals. The contents of IgG, IgM, IgA immunoglobulins, and sIgA in the vaginal secretion were determined by radial immunodiffusion (Mancini technique). \u0000On the 14th day of the experiment, a significant increase in the IgG contents and decreased levels of IgM and IgA were observed in the blood of the cows from experimental group. However, these indexes still remained lower than in healthy cows. In vaginal secretions, a significant decrease in the IgM and sIgA amounts was detected. The immunoglobulin levels in vaginal secretions after antibiotic therapy did not differ from the healthy cows. \u0000The use of tulathromycin for treatment of genital mycoplasmosis in pregnant cows shows high therapeutic efficacy, but does not lead to a complete normalization of their immunoglobulin status.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83886491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-1210-mip
D. Grebennikov, Valeriya V. Zheltkova, R. Savinkov, G. Bocharov
The immune system is a complex multiscale multiphysical object. Understanding its functioning in the frame of systemic analysis implies the use of mathematical modelling, formulation of data consistency criterion, estimation of parameters, uncertainty analysis, and optimal model selection. In this work, we present some promising approaches to modelling the multi-physics immune processes, i.e., cell migration in lymph nodes (LN), lymph flow, homeostatic regulation of immune responses in chronic infections. To describe the spatial-temporal dynamics of immune responses in lymph LN, we propose a model of lymphocyte migration, based on the second Newtons law and considering three kinds of forces. The empirical distributions of three lymphocytes motility characteristics were used for model calibration using the KolmogorovSmirnov metric. Prediction of lymph flow in a lymph node requires costly computations, due to diversity of sizes, forms, inner structure of LNs and boundary conditions. We proposed an approach to lymph flow modelling based on replacing the full-fledged computational physics-based model with an artificial neural network (ANN), trained on the set of pre-formed results computed using an initial mechanistic model. The ANN-based model reduces the computational time for some lymph flow characteristics by four orders of magnitude. Calibration of MarchukPetrov model of antiviral immune response for SARS-CoV-2 infection was performed. To this end, we used previously published data on the viral load kinetics in nasopharynx of volunteers, and data on the observed ranges of interferon, antibodies and CTLs in the blood. The parameters, which have the most significant impact at different stages of infection process, were identified. Inhibition of immune mechanisms, e.g., T cell exhaustion, is a distinctive feature of chronic viral infections and malignant diseases. We propose a mathematical model for the studies of regulation parameters of four exhausted T cell subsets in order to examine the balance of their proliferation and differentiation determined by interaction with SIRPa+ PD-L1+ and XCR+1 dendritic cells. The model parameters are evaluated, in order to study the reinvigoration effect of aPD-L1 therapy on the homeostasis of exhausted cells.
{"title":"Mathematical immunology: processes, models and data assimilation","authors":"D. Grebennikov, Valeriya V. Zheltkova, R. Savinkov, G. Bocharov","doi":"10.46235/1028-7221-1210-mip","DOIUrl":"https://doi.org/10.46235/1028-7221-1210-mip","url":null,"abstract":"The immune system is a complex multiscale multiphysical object. Understanding its functioning in the frame of systemic analysis implies the use of mathematical modelling, formulation of data consistency criterion, estimation of parameters, uncertainty analysis, and optimal model selection. In this work, we present some promising approaches to modelling the multi-physics immune processes, i.e., cell migration in lymph nodes (LN), lymph flow, homeostatic regulation of immune responses in chronic infections. \u0000To describe the spatial-temporal dynamics of immune responses in lymph LN, we propose a model of lymphocyte migration, based on the second Newtons law and considering three kinds of forces. The empirical distributions of three lymphocytes motility characteristics were used for model calibration using the KolmogorovSmirnov metric. \u0000Prediction of lymph flow in a lymph node requires costly computations, due to diversity of sizes, forms, inner structure of LNs and boundary conditions. We proposed an approach to lymph flow modelling based on replacing the full-fledged computational physics-based model with an artificial neural network (ANN), trained on the set of pre-formed results computed using an initial mechanistic model. The ANN-based model reduces the computational time for some lymph flow characteristics by four orders of magnitude. \u0000Calibration of MarchukPetrov model of antiviral immune response for SARS-CoV-2 infection was performed. To this end, we used previously published data on the viral load kinetics in nasopharynx of volunteers, and data on the observed ranges of interferon, antibodies and CTLs in the blood. The parameters, which have the most significant impact at different stages of infection process, were identified. \u0000Inhibition of immune mechanisms, e.g., T cell exhaustion, is a distinctive feature of chronic viral infections and malignant diseases. We propose a mathematical model for the studies of regulation parameters of four exhausted T cell subsets in order to examine the balance of their proliferation and differentiation determined by interaction with SIRPa+ PD-L1+ and XCR+1 dendritic cells. The model parameters are evaluated, in order to study the reinvigoration effect of aPD-L1 therapy on the homeostasis of exhausted cells.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74393192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-12362-nas
K. A. Khlystova, N. G. Sarkisyan, N. Kataeva
Antimicrobial function of innate immunity is mediated by the low-molecular weight peptides which are active against bacteria, fungi and some viruses. The review presents data on studies of both natural and synthetic peptides regarding the features of their structure and therapeutic effect. As a rule, the molecules of such peptides are positively charged, due to amino acid radicals capable of protonation. Spatially, antimicrobial peptide molecules are arranged as -helices or -layers in separate or compound assemblies. At the same time, short molecular chains, including up to 18 amino acid residues, exist as a linear or cyclic forms, remaining at the level of primary spatial structure. Natural antimicrobial peptides are predominantly produced by neutrophilic granulocytes and macrophages, as well as epithelial cells of the barrier organs. Three families of natural antimicrobial peptides have been most studied: defensins, cathelicidins, and histatins. Defensins are active against Gram-positive and Gram-negative bacteria, viruses and fungi, having anti-inflammatory and immunomodulatory activity. Cathelicidins are chemoattractants and exert antibacterial, immunomodulatory, wound healing, antitumor effects, potentially contributing to the development of autoimmune diseases. Histatins have a pronounced fungicidal effect and prevent the formation of bacterial biofilms. A detailed study on the structure and principles of action of natural antimicrobial peptides made it possible to apply this information for the in vitro synthesis of peptides thus making it possible to create multipurpose drugs based on them. E.g., synthetic peptides WR12 and D-IK8 ensure the delivery of antibiotics to infected or tumor cells, due to permeabilization of cellular membranes. At the same time, a synthetic peptide, acipensin 1, is capable of penetrating into human tumor cells without damaging them. The immunomodulatory peptide glutoxim is effectively used in anti-tuberculosis therapy. ZP2 peptide, the functional site of granulocyte-macrophage colony-stimulating factor is effective against Gram-negative bacteria (K. pneumoniae, P. aeruginosa and A. baumannii) as well as EpsteinBarr virus. Thymic immunoregulatory peptides bestim, hepon, thymogen and imunofan are inducers of endogenous - and -interferon production, inhibit the development of malignant neoplasms, and possess anti-inflammatory activity. Gepon is used in the treatment of viral hepatitis, respiratory and opportunistic infections, croup syndrome and sexually transmitted infections (including genital herpes). Thus, the synthetic antimicrobial peptides are widely used in complex treatment regimens along with conventional antibiotics, antiviral, and antitumor drugs, thus making it possible to achieve higher therapeutic effect.
{"title":"Natural and synthetic peptides in antimicrobial therapy","authors":"K. A. Khlystova, N. G. Sarkisyan, N. Kataeva","doi":"10.46235/1028-7221-12362-nas","DOIUrl":"https://doi.org/10.46235/1028-7221-12362-nas","url":null,"abstract":"Antimicrobial function of innate immunity is mediated by the low-molecular weight peptides which are active against bacteria, fungi and some viruses. The review presents data on studies of both natural and synthetic peptides regarding the features of their structure and therapeutic effect. As a rule, the molecules of such peptides are positively charged, due to amino acid radicals capable of protonation. Spatially, antimicrobial peptide molecules are arranged as -helices or -layers in separate or compound assemblies. At the same time, short molecular chains, including up to 18 amino acid residues, exist as a linear or cyclic forms, remaining at the level of primary spatial structure. Natural antimicrobial peptides are predominantly produced by neutrophilic granulocytes and macrophages, as well as epithelial cells of the barrier organs. Three families of natural antimicrobial peptides have been most studied: defensins, cathelicidins, and histatins. Defensins are active against Gram-positive and Gram-negative bacteria, viruses and fungi, having anti-inflammatory and immunomodulatory activity. Cathelicidins are chemoattractants and exert antibacterial, immunomodulatory, wound healing, antitumor effects, potentially contributing to the development of autoimmune diseases. Histatins have a pronounced fungicidal effect and prevent the formation of bacterial biofilms. A detailed study on the structure and principles of action of natural antimicrobial peptides made it possible to apply this information for the in vitro synthesis of peptides thus making it possible to create multipurpose drugs based on them. E.g., synthetic peptides WR12 and D-IK8 ensure the delivery of antibiotics to infected or tumor cells, due to permeabilization of cellular membranes. At the same time, a synthetic peptide, acipensin 1, is capable of penetrating into human tumor cells without damaging them. The immunomodulatory peptide glutoxim is effectively used in anti-tuberculosis therapy. ZP2 peptide, the functional site of granulocyte-macrophage colony-stimulating factor is effective against Gram-negative bacteria (K. pneumoniae, P. aeruginosa and A. baumannii) as well as EpsteinBarr virus. Thymic immunoregulatory peptides bestim, hepon, thymogen and imunofan are inducers of endogenous - and -interferon production, inhibit the development of malignant neoplasms, and possess anti-inflammatory activity. Gepon is used in the treatment of viral hepatitis, respiratory and opportunistic infections, croup syndrome and sexually transmitted infections (including genital herpes). Thus, the synthetic antimicrobial peptides are widely used in complex treatment regimens along with conventional antibiotics, antiviral, and antitumor drugs, thus making it possible to achieve higher therapeutic effect.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78323411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07DOI: 10.46235/1028-7221-12430-foh
E. Kostolomova, S. Strelin, Yurij Sukhovei, I. Unger, T. V. Akuneeva, Alexander A. Markov, Elizaveta D. Polyanskikh
Currently, the treatment of persistent non-healing wounds is among the most difficult clinical issues. We studied 20 samples of normal human skin, 10 specimens from patients with acute trauma, and 9 samples from the patients with chronic wounds that did not heal within 2 months. Using multicolor flow cytometry, we found that the resident T lymphocytes (CD3++ and CD3++) are able to locally produce biologically active substances, normalize human skin homeostasis, thus promoting the wound healing. The data obtained indicate that the blood contains mainly +T lymphocytes (p 0.001), while the +T cells detected in wounds represent a population similar to skin cells. We found no difference in the ratio of resident T cells in chronic and acute wounds, and healthy epithelium. Accordingly, non-healing of wounds and chronic clinical course may be caused by dysfunction of T cells. CD69 regulates T cell secretion of growth factors, IFN, IL-17 and IL-22. The relative number of CD69-expressing T cells from the patients with acute wounds was significantly increased, if compared with cells from normal epidermis and chronic wounds (10.5%2.3, 7.6%1.24, and 3.0%1.05, respectively. p 0.001). The number of cells with the CD3++CD69+ phenotype did not differ significantly between all three groups under comparison. Dysregulation of T cell-mediated healing in chronic wounds is caused by reduced production of IGF-1 by resident CD3++T lymphocytes (1.7%0.9 (p 0.001), and CD3++ (0.44%0.02, p 0.001) compared to CD3++T cells derived from acute wounds (13.6%5.6) and CD3++ (8.9%3.1). The + and + T cells isolated from non-healing chronic wounds did not respond to mitogenic stimuli, unlike the cells obtained from acute wounds and healthy skin. In vitro analysis of cytokine secretion by the CD69-deficient dermal T cells showed a lower spontaneous secretion of IL-22 (4.56%2.3 and 23.9%1.05 and 10.6%1.24, respectively; p 0.001) and IL-2 (0.9%0.08 and 22.6%2.5 and 3.9%1.0, and respectively; p 0.01). When analyzing the number of resident skin T cells secreting IL-17, we obtained the following differences for healthy skin (1.4%0.08), acute wounds (11.3%3.2) and chronic wounds (31.7%11.8), thus showing a significant intergroup difference (p 0.001). T lymphocytes in chronic wounds exhibit some functional disorders and are not able to produce biologically active substances that promote physiological tissue regeneration. The results suggest a role of resident T cells in human skin in wound healing processes and provide new insights into the pathogenesis of chronic wounds.
{"title":"Function of human skin T cells in wound healing in the in vitro experimental setting","authors":"E. Kostolomova, S. Strelin, Yurij Sukhovei, I. Unger, T. V. Akuneeva, Alexander A. Markov, Elizaveta D. Polyanskikh","doi":"10.46235/1028-7221-12430-foh","DOIUrl":"https://doi.org/10.46235/1028-7221-12430-foh","url":null,"abstract":"Currently, the treatment of persistent non-healing wounds is among the most difficult clinical issues. We studied 20 samples of normal human skin, 10 specimens from patients with acute trauma, and 9 samples from the patients with chronic wounds that did not heal within 2 months. Using multicolor flow cytometry, we found that the resident T lymphocytes (CD3++ and CD3++) are able to locally produce biologically active substances, normalize human skin homeostasis, thus promoting the wound healing. The data obtained indicate that the blood contains mainly +T lymphocytes (p 0.001), while the +T cells detected in wounds represent a population similar to skin cells. We found no difference in the ratio of resident T cells in chronic and acute wounds, and healthy epithelium. Accordingly, non-healing of wounds and chronic clinical course may be caused by dysfunction of T cells. CD69 regulates T cell secretion of growth factors, IFN, IL-17 and IL-22. The relative number of CD69-expressing T cells from the patients with acute wounds was significantly increased, if compared with cells from normal epidermis and chronic wounds (10.5%2.3, 7.6%1.24, and 3.0%1.05, respectively. p 0.001). The number of cells with the CD3++CD69+ phenotype did not differ significantly between all three groups under comparison. Dysregulation of T cell-mediated healing in chronic wounds is caused by reduced production of IGF-1 by resident CD3++T lymphocytes (1.7%0.9 (p 0.001), and CD3++ (0.44%0.02, p 0.001) compared to CD3++T cells derived from acute wounds (13.6%5.6) and CD3++ (8.9%3.1). The + and + T cells isolated from non-healing chronic wounds did not respond to mitogenic stimuli, unlike the cells obtained from acute wounds and healthy skin. In vitro analysis of cytokine secretion by the CD69-deficient dermal T cells showed a lower spontaneous secretion of IL-22 (4.56%2.3 and 23.9%1.05 and 10.6%1.24, respectively; p 0.001) and IL-2 (0.9%0.08 and 22.6%2.5 and 3.9%1.0, and respectively; p 0.01). When analyzing the number of resident skin T cells secreting IL-17, we obtained the following differences for healthy skin (1.4%0.08), acute wounds (11.3%3.2) and chronic wounds (31.7%11.8), thus showing a significant intergroup difference (p 0.001). T lymphocytes in chronic wounds exhibit some functional disorders and are not able to produce biologically active substances that promote physiological tissue regeneration. The results suggest a role of resident T cells in human skin in wound healing processes and provide new insights into the pathogenesis of chronic wounds.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85360844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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