Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients.
Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients.
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DOI：
10.1371/journal.pone.0078686
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rufer N
中科院分区：
文献类型：
--
作者：
Iancu EM;Gannon PO;Laurent J;Gupta B;Romero P;Michielin O;Romano E;Speiser DE;Rufer N
持久性病毒被特定的淋巴细胞所控制。抗eb病毒（EBV）的克隆T细胞受体（TCR）库一旦在初次感染后建立，随着时间的推移表现出强大的稳定性。然而，促成这种长期持续的决定因素仍然缺乏特征。利用体内淋巴细胞稳态被短暂扰乱的临床环境，我们研究了EBV抗原特异性CD8 T细胞在黑色素瘤患者非清髓性淋巴消耗化疗前后的变化。尽管T细胞分化更先进，但患者T细胞的克隆组成与健康个体相当，对TRBV20和TRBV29基因片段的使用和几种共同显性的公共TCR克隆型具有相同的偏好。此外，我们的数据显示，相对较少的显性EBV抗原特异性T细胞克隆型存在，这些克隆型大多在短暂性淋巴细胞耗损（TLD）和淋巴细胞恢复后持续存在，可能与这些患者缺乏EBV再激活和新生T细胞启动有关。有趣的是，持久的克隆型经常共同表达记忆/归巢相关基因（CD27、IL7R、EOMES、CD62L/SELL和CCR5），这支持了它们对持久的CD8 T细胞反应特别重要的观点。然而，ebv特异性CD8 T细胞的克隆组成在非清髓性化疗后随着时间的推移而保持相同的显性克隆型。观察到的克隆型持久性表明CD8 T细胞稳态和重构的高稳健性。
Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution.
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DOI：
10.1038/nrc3322
发表时间：
2012-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gattinoni L;Klebanoff CA;Restifo NP
通讯作者：
Restifo NP
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
4.1
作者：
Fonseca, Simone G.;Procopio, Francesco A.;Sekaly, Rafick-Pierre
通讯作者：
Sekaly, Rafick-Pierre
影响因子：
4.4
作者：
Iancu, Emanuela M.;Corthesy, Patricia;Rufer, Nathalie
通讯作者：
Rufer, Nathalie
影响因子：
45.3
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA