Russian journal of immunology : RJI : official journal of Russian Society of Immunology最新文献

The year 2002 has been, probably, the most complicated and eventful in the short history of the RJI. During that year many projects planned by the Editorial Board in the beginning-middle of the year 2001 started to become a reality. Unfortunately, one of the main initiators of these projects - Editor-in-Chief of the RJI, Professor Anatoly N. Cheredeev - cannot witness this success. On May 3rd, 2003 it will be a year since A.N. Cheredeev died. One of the important projects that we have accomplished is the creation of a joint Internet site of the RSI and the RJI that provides online access to the full text of articles of the journal. Although this «Russian Immunology» site (www.rji.ru) still needs a lot of work, it already takes a noteworthy place among other immunology resources on the Internet. The number of visitors of this site increased in four times during 2002, reaching more than 1500 users a month. A second important project accomplished during the past year has been the inclusion of the RJI to the biggest international bibliographic databases. At the beginning of 2002 the RJI was added to the list of indexed and cited journals of the oldest database - the Chemical Abstracts. In addition, we are glad to announce that the complete archive of articles published in the RJI has just been added to the most popular and visited bibliographic database, the Index Medicus/Medline/PubMed. Following the tradition every two years the RJI makes changes in the Editorial Board. The reasons for these changes are the advances in the field of Immunology, the establishment of new research directions, the opening of new laboratories, and the appearance of new scientific leaders. The incorporation of these new leaders into the Editorial Board improves the journal productivity, making the review process more effective and attracting new interesting authors. We would like to introduce the new members of our Editorial Board.

Photodynamic therapy is frequently accompanied by the induction of immunosuppression. The photochemical mechanisms behind the induction of this immunosuppression are not clear. The purpose of this study was to evaluate the potential of photoproducts of merocyanine 540 (MC540), protoporphyrin IX (PPIX) and hematoporphyrin derivative (HpD) to cause modulation (suppression/activation) of the T cell immune response in vivo. The approach that we have adopted is the pre-irradiation of a photosensitizer solution with the subsequent application of the products of photosensitizer photodegradation in animals. In this approach the photochemical mechanisms of type I and II are not involved in the photosensitized modification of biological targets in vivo. Using the model of delayed type hypersensitivity (DTH) reaction to sheep red blood cells in mice, we have demonstrated that the photoproducts of three essentially different photosensitizers affect T-cell immunity. The HpD photoproducts had a suppressive effect on the DTH, while products of PPIX photodegradation enhanced the DTH nearly twice. Pre-irradiated MC540 strongly modulated the DTH response, i.e. the DTH was enhanced at low doses and inhibited at higher doses. Our results strongly indicate that at least part of the photodynamic therapy-induced immunomodulation may occur via the photobleaching of photosensitizers accompanied by the generation of photoproducts, which can affect T cell immunity.

It is well known that the enhancement of the cell-matrix interactions represents one of the early steps in the process of lymphocyte activation. However, the information regarding the role of these interactions in the late stages of lymphocyte activation (in particular, the proliferation) is still controversial. This is basically due to the absence of adequate experimental models. In the present work we carried out a step-by-step modification of a well-studied model of mitogen-stimulated lymphocyte activation, adjusting it to the conditions of a three-dimensional collagen matrix (3D-CM). All the changes added to the standard procedure in the process of this modification were rigorously controlled using various experimental models. The final version of the method includes the following steps: (i) 24-h lymphocyte (lymphocyte fraction from mouse spleen) preincubation with mitogens (Con A or LPS) with a subsequent cell wash (parameters being controlled: irreversible lymphocyte activation, independence of the proliferation from cell-cell interactions); (ii) transfer of the activated lymphocytes to (3)H-thymidine containing 3D-CM and incubation for 48 h (controlled parameters: distribution of the radioactive label within the 3D-CM and its biological accessibility to lymphocytes); (iii) degradation of the 3D-CM with bacterial collagenase and cell transfer onto glass fiber filters (controlled parameters: cell viability after cultivation in the 3D-CM and treatment with the collagenase). With this method we found that the proliferation of the Con A- and LPS-stimulated lymphocytes in 3D-CM was dramatically inhibited (by 66.5 +/- 14.9% and by 88.1 +/- 10.2%, respectively). The discovered inhibition of the lymphocyte proliferation was not a consequence of either the ineffectiveness of the mitogens, the disruption of the cell-cell interactions, an insufficient inclusion of the radioactive label into cells, or of a decreased cell viability.

The rate of transition from one stage to another during the course of HIV infection is characterized by changes in the cytokine network balance. The alterations in the cytokine network balance during HIV infection depend on the individual profile of cytokine production predetermined by the functioning of the genes encoding the immunomodulators. The purpose of this research is to study the distribution in the frequency of allelic variants of the promoter regions of the genes encoding pro-inflammatory (T-330G IL2 and G-308A TNFA) and anti-inflammatory (C-590T IL4 and C-597A IL10) cytokines among healthy individuals of European origin and in HIV-infected patients with various rates of HIV progression (fast and slow). Four polymorphic loci of the promoter regions were analyzed in 127 HIV-infected patients and 52 healthy individuals using the polymerase chain reaction - restriction light fragment polymorphism (PCR-RLFP) methodology. We have obtained data indicating an increased allelic content of genotypes T/T IL2 (OR = 1.67), G/A TNFA (OR = 4.21), T/T IL4 (OR = 3.43), C/A IL10 (OR = 1.34) in HIV-infected patients as compared to healthy individuals. The correlation between the genotypes and allelic combinations of the investigated cytokines, and the rate of the infection progression in AIDS has been investigated. The association of T/G IL2, G/A TNFA, T/T IL4, A/A IL10 allelic variants of the immunomodulator genes with a fast rate of HIV infection has been established.

Children with attention deficit syndrome with hyperactivity (ADSH) are characterised by attention and motor deficiencies and obvious immune disorders, which manifest as recurrent acute viral respiratory tract infections and changes in immunological parameters. It was established that the structure of deviations in the spectrum of elements in children with ADSH has characteristic features. The atomic emission analysis of cerebrolysin detected an advantageous combination of trace elements with neuroactive and antioxidant properties. The effect of cerebrolysin on immunological parameters was studied in vitro and in vivo. Cerebrolysin was administered in a dose of 1 ml per 10 kg of weight intramuscularly during 1 month. The administration of cerebrolysin resulted in a simultaneous normalization of neurological and immune disorders and in a reduction in the illness rate. In in vitro experiments cerebrolysin enhanced the expression of activation markers (HLA DR, CD25) by CD45(+)CD14(-) lymphocytes, particularly by CD4(+) cells. In vivo it led to the normalization of the numbers of CD4(+), CD19(+), CD16(+) and CD56(+) cells and of the level of serum IgG and IgA. Cerebrolysin normalized the expression of HLA DR molecules on the surface of CD8(+) cells and increased the amount of CD11b(+) lymphocytes. At the same time, it did not affect the level of CD95 molecule expression.

Strong immunosuppression occurs after severe traumatic brain injury (TBI) and most likely contributes substantially to the patient morbidity and mortality. However, the mechanisms of this immunosuppression are unknown. For the lowering of stressful factors, severe TBI was induced in anaesthetized rats. The lymphocyte subsets from 60 rats with severe TBI were analyzed using monoclonal antibody by the indirect immunofluorescence method. The blood of 30 rats without TBI was used as a control. When compared to the control group, the rats with TBI showed a remarkable reduction in the relative number of CD4(+), RT-Ia(+), Thy-1(+) and ICO-111(+) lymphocytes during the first 2 h after injury. Further reduction in the number of CD4(+) cells was determined in the rats during all the period of the experimental observation. The number of lymphocytes expressing membrane Thy-1 and ICO-111 antigens was significantly decreased 7 days after the trauma. The relative number of RT-Ia(+) lymphocytes was significantly reduced in rats with TBI during 14 days following the trauma. A significant decrease in the luminescence intensity of all the analyzed antigen-positive cells was also observed in rats with TBI. Between the 7th and the 14th days after the trauma a positive correlation between the number of Thy-1(+) PBLs and the number of RT-Ia(+) lymphocytes was determined. Similar results on lymphocyte immunophenotype were seen in patients with TBI. Thus, the cellular immune response is identical in patients and in animals with TBI. Severe brain traumatic injury leads to a reduced expression of cell surface antigens and causes a decrease in the number of antigen-positive lymphocytes and in the intensity of their luminescence.

Myocarditis (MC) is an inflammation of the cardiac muscle. Viral infections appear to be the most frequent cause for induction of MC. According to the I. Roitt's classification, autoimmune (AI) MC is an organ-specific form of AI pathology. Thus, autoreactive antibodies (auto-Abs) against myocardial antigens and autoreactive T cells are major pathogenic mechanisms, and they are a common cause of cardiac muscle disorder progression. The autoantigens from myocardial tissue (like cardiomyosin and etc.) and/or the phenomena of virus mimicry stimulate auto-Ab production and their cross-reactivity with myocardial antigens. Some auto-Abs in patients with AI diseases demonstrate DNA-hydrolytic or proteolytic abilities against autoantigen. We found both DNA-abzymes and protabzymes in some MC patients. They showed catalytic activity not only against non-specific polypeptide, but also specific activity against cardiomyosine. Proteolytic activities of protabzymes differ depending on the clinical form and activity of MC. This suggests a role of protabzymes in the pathogenesis of AI-MC. According to some authors, auto-Abs (including auto-Abs with catalytic ability) in patients with AI diseases can be additional regulatory factors of apoptosis.

As an extension of our investigation of the mechanisms of regulation of NK cell activity we have compared the integral parameters of NK cell cytotoxicity (IPC) and IFN production (IPIP) measured as the square of the area under the cytotoxic and IFN titer functional curves. They were compared with the parameters obtained by the standard effector : target cell (E:T) ratio method. The calculations were done in groups of healthy individuals, PBL of which are distinguished by the levels of NK cell cytotoxicity and IFN production measured in the reaction of natural cytotoxicity. For the calculation of the difference, we used data from individuals with values of the IPC and IPIP higher or lower than the mean values. It has been shown that the "changes" in IPC and IPIP are not proportional. The variations in the NK cytotoxicity were 13-45%, while the differences in IFN titer were 38-69% as compared to the mean values. This analysis revealed a negative correlation between the variations corresponding to some E:T ratios. The correlation coefficients varied between -0.07 and -0.28, suggesting a weak negative association between the compared parameters. Thus, the approach used in this work helped us to develop experimental conditions that revealed a negative correlation between NK cell cytotoxicity and IFN production by normal human PBL.

Animal models that mimic the whole spectrum of susceptibility and resistance of human populations to tuberculosis would be useful for studying pathogenesis of tuberculosis, mechanisms of the host defense, and for testing prospective prophylactic and therapeutic tuberculosis vaccines and drugs. Inbred mouse strains are broadly and successfully used to model human tuberculosis and study mechanisms of host-mycobacteria interaction. Here we consider numerous aspects of murine models of tuberculosis. We analyze the course of tuberculosis depending on route and dosage of mycobacterial infection, and discuss the conformity of these approaches to the natural route of human infection. The advantage of the mouse model is provided by the availability of hundreds of inbred strains with different genetic background. It allows a genetic analysis of the mouse susceptibility/resistance to tuberculosis. Mouse strains with specific properties such as congenic, recombinant, recombinant inbred, recombinant congenic, mutant and usage of whole genome screening led to mapping loci controlling these traits. Transgenic mouse strains with gene insertion or targeted mutation (knock-out of a gene) are very effective tools for studying the role of specific genes controlling the anti-tuberculosis immunity. Mice with knock-out genes for cytokines, chemokines, cell subpopulations, cell receptors, and enzymes are broadly used to identify the mechanisms of tuberculosis control. In this review we examine a mouse model for anti-tuberculosis vaccine and drug testing. In addition, we present some important phenomena of tuberculosis immunity - latent tuberculosis/reactivation and immunological memory to tuberculosis.