Implication of γδ T cells in the human immune response to cytomegalovirus
Implication of γδ T cells in the human immune response to cytomegalovirus
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DOI：
10.1172/jci5409
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发表时间：
1999-05-01
影响因子：
15.9
通讯作者：
Moreau, JF
中科院分区：
文献类型：
--
作者：
Déchanet, J;Merville, P;Moreau, JF
在正常个体中，γ δ T细胞占总外周T淋巴细胞的不到6%，并且主要表达T细胞受体（TCR）V δ 2-V γ 9链。我们以前曾观察到，只有当肾移植受者发生巨细胞病毒（CMV）感染时，其外周血中γ δ T细胞才急剧扩增，这种扩增持续时间较长（超过1年），与γ δ T细胞的活化有关，并且仅涉及V δ 1或V δ 3 T细胞亚群。γ δ TCR连接多样性的分析显示，这些患者中的CMV感染伴随着（a）V δ 3中的CDR 3大小分布的显著限制，以及在较小程度上，V δ 1链中的CDR 3大小分布的显著限制;以及（B）携带复发性连接氨基酸基序的V δ 1细胞的选择性扩增。这些特征高度提示在CMV感染过程中γ δ T细胞亚群的体内抗原驱动选择。此外，来自CMV感染的肾受体的V δ 1和V δ 3 T细胞能够在游离CMV或CMV感染的成纤维细胞裂解物存在下体外增殖，但不能在未感染或其他疱疹病毒感染的成纤维细胞裂解物存在下增殖，这种体外扩增被抗γ δ TCR mAb抑制。这些发现表明γ δ T细胞群可能在免疫抑制患者对CMV感染的免疫应答中起重要作用。
In normal individuals, gamma delta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) V delta 2-V gamma 9 chains. We have previously observed a dramatic expansion of gamma delta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection, This increase was long lasting (more than 1 year), was associated with an activation of gamma delta T cells, and concerned only V delta 1 or V delta 3 T-cell subpopulations. Analysis of gamma delta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in V delta 3 and, to a lesser extent, in V delta 1 chains; and (b) a selective expansion of V delta 1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gamma delta T-cell subsets during the course of CMV infection, Furthermore, V delta 1 and V delta 3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates, This in vitro expansion was inhibited by anti-gamma delta TCR mAb's, These findings suggest that a population of gamma delta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.