Ricardo Cuesta-Martín de la Cámara, Andrea Torices-Pajares, Laura Miguel-Berenguel, Keren Reche-Yebra, Esteban Frauca-Remacha, Loreto Hierro-Llanillo, Gema Muñoz-Bartolo, María Dolores Lledín-Barbacho, Almudena Gutiérrez-Arroyo, Ana Martínez-Feito, Eduardo López-Granados, Elena Sánchez-Zapardiel
{"title":"小儿肝移植受者的 Epstein-Barr 病毒特异性 T 细胞反应：多参数流式细胞术横断面研究。","authors":"Ricardo Cuesta-Martín de la Cámara, Andrea Torices-Pajares, Laura Miguel-Berenguel, Keren Reche-Yebra, Esteban Frauca-Remacha, Loreto Hierro-Llanillo, Gema Muñoz-Bartolo, María Dolores Lledín-Barbacho, Almudena Gutiérrez-Arroyo, Ana Martínez-Feito, Eduardo López-Granados, Elena Sánchez-Zapardiel","doi":"10.3389/fimmu.2024.1479472","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.</p><p><strong>Methods: </strong>Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-S<sup>NEG</sup>, IP-S<sup>POS</sup>VL<sup>NEG</sup> and IP-S<sup>POS</sup>VL<sup>POS</sup> groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator<sup>®</sup>) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency.</p><p><strong>Results: </strong>Polyfunctional CD8+ T cells indicated previous EBV contact (IP-S<sup>NEG</sup> 0.00% vs IP-S<sup>POS</sup> 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-S<sup>NEG</sup> 0.01% vs IP-S<sub>POS</sub> 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-S<sup>POS</sup>VL<sup>POS</sup> 0.43% vs IP-S<sup>POS</sup>VL<sup>NEG</sup> 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-S<sup>NEG</sup> 0.00% vs IP-S<sup>POS</sup> 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-S<sup>NEG</sup> patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-S<sup>POS</sup>VL<sup>POS</sup> patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81).</p><p><strong>Conclusion: </strong>Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540634/pdf/","citationCount":"0","resultStr":"{\"title\":\"Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.\",\"authors\":\"Ricardo Cuesta-Martín de la Cámara, Andrea Torices-Pajares, Laura Miguel-Berenguel, Keren Reche-Yebra, Esteban Frauca-Remacha, Loreto Hierro-Llanillo, Gema Muñoz-Bartolo, María Dolores Lledín-Barbacho, Almudena Gutiérrez-Arroyo, Ana Martínez-Feito, Eduardo López-Granados, Elena Sánchez-Zapardiel\",\"doi\":\"10.3389/fimmu.2024.1479472\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.</p><p><strong>Methods: </strong>Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-S<sup>NEG</sup>, IP-S<sup>POS</sup>VL<sup>NEG</sup> and IP-S<sup>POS</sup>VL<sup>POS</sup> groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator<sup>®</sup>) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency.</p><p><strong>Results: </strong>Polyfunctional CD8+ T cells indicated previous EBV contact (IP-S<sup>NEG</sup> 0.00% vs IP-S<sup>POS</sup> 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-S<sup>NEG</sup> 0.01% vs IP-S<sub>POS</sub> 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-S<sup>POS</sup>VL<sup>POS</sup> 0.43% vs IP-S<sup>POS</sup>VL<sup>NEG</sup> 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-S<sup>NEG</sup> 0.00% vs IP-S<sup>POS</sup> 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-S<sup>NEG</sup> patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-S<sup>POS</sup>VL<sup>POS</sup> patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81).</p><p><strong>Conclusion: </strong>Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.</p>\",\"PeriodicalId\":12622,\"journal\":{\"name\":\"Frontiers in Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540634/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fimmu.2024.1479472\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2024.1479472","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：EB病毒（Epstein-Barr virus，EBV）特异性T细胞应答测定有助于调整持续感染的移植患者的免疫抑制。我们的目的是在一组小儿肝移植患者中确定针对 EBV 的 T 细胞反应：我们的横断面研究纳入了 38 名免疫抑制小儿肝移植患者（IP）和 25 名 EBV 血清阳性健康成人对照组（HC）。根据患者的 EBV 血清学（S）和病毒载量（VL）状态，将其分为 IP-SNEG 组、IP-SPOSVLNEG 组和 IP-SPOSVLPOS 组。在两个时间点用 EBV 肽（PepTivator®）刺激细胞，并进行细胞内细胞因子和活化诱导标记染色，以评估 T 细胞反应。使用背景减法确定 EBV 特异性 T 淋巴细胞的频率：结果：多功能 CD8+ T 细胞表明曾接触过 EBV（IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%；分别为 p=0.001 和 p=0.01）。血清学阳性（IP-SNEG 0.01% vs IP-SPOS 0.13% 和 HC 0.03%；分别为 p=0.01 和 p=0.50）和病毒载量阳性（IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% 和 HC 0.03%；分别为 p=0.03 和 p=0.001）患者的 CD8+CD107a+IFNɣ+IL2-TNFα- 多功能特征增加。血清学阳性成人的中央记忆细胞有所增加（IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; 分别为 p=0.58 和 p=0.002）。在第二个时间点，IP-SNEG 患者仍为阴性（首次就诊 0.01% vs 第二次就诊 0.00%，p=0.44）。另一方面，IP-SPOSVLPOS 患者的病毒载量清除，多功能 CD8+CD107a+IFNɣ+IL2-TNFα- 细胞随之减少（第一次就诊时为 0.43% vs 第二次就诊时为 0.10%，p=0.81）：结论：多功能 CD8+ EBV 特异性 T 细胞反应可检测肝移植儿童是否曾接触过 EBV。CD8+CD107a+IFNɣ+IL2-TNFα-%在病毒载量呈阳性的患者中增加。中心记忆 CD4+ T 细胞群能更有效地确定成人是否曾接触过 EBV。
Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.
Background: Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.
Methods: Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency.
Results: Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81).
Conclusion: Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.
期刊介绍：
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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