Human T-cell memory consists mainly of unexpanded clones
Human T-cell memory consists mainly of unexpanded clones
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DOI：
10.1016/j.imlet.2010.06.011
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发表时间：
2010-09-06
影响因子：
4.4
通讯作者：
de Vries, Niek
中科院分区：
文献类型：
--
作者：
Klarenbeek, Paul L.;Tak, Paul P.;de Vries, Niek
免疫系统能够使用适应性受体（包括 αβ-T 细胞受体 (TCR)）对数百万种抗原做出反应。一旦遇到抗原，T 细胞可能会增殖，产生 TCR 相同细胞的克隆，从而形成记忆表型。先前的研究表明，大多数记忆克隆都有明显的扩展。据报道，T 细胞记忆亚群的 β 链库的多样性比幼稚亚群低 10 倍，这反映了严格的选择。然而，由于技术限制，缺乏关于克隆扩增的大小以及幼稚和记忆 T 细胞群中 TCR 库多样性的详细信息。在这里，我们使用高通量测序表明，人类外周血中的记忆库仅包含少量扩展克隆，并且主要由低频克隆组成。此外，记忆库比预期更加多样化。在两名健康人中，我们观察到只有 2-7% 的 CD4 和 CD8 记忆克隆明显扩增。根据这一观察，我们发现 CD4 记忆区室的 β 链库大小仅比原始区室小两倍，而 CD8 记忆区室的 β 链库大小仅小 3-10 倍。我们的结果表明，T 细胞记忆区室的克隆分布与预期截然不同。这对当前免疫记忆的教条具有重要意义，并改变了对（病理）生理情况（例如衰老和自身免疫）中所有指令畸变的解释。它对引导记忆表型成熟和决定记忆克隆大小的因素提出了新的问题。 (C) 2010 Elsevier B.V. 保留所有权利。
The immune system is able to respond to millions of antigens using adaptive receptors, including the alpha beta-T-cell receptor (TCR). Upon antigen encounter a T-cell may proliferate to produce a clone of TCR-identical cells, which develop a memory phenotype. Previous studies suggested that most memory clones are clearly expanded. In accordance, the beta-chain repertoire of T-cell memory subsets was reported to be 10 times less diverse than those of naive subsets, reflecting stringent selection. However, due to technological limitations detailed information was lacking regarding the size of clonal expansions and the diversity of the TCR-repertoire in naive and memory T-cell populations. Here, using high-throughput sequencing, we show that the memory repertoire in human peripheral blood contains only few expanded clones and consists mainly of low frequency clones. Additionally, the memory repertoire is much more diverse than expected. In two healthy persons we observed that only 2-7% of the CD4 and CD8 memory clones found were clearly expanded. In line with this observation we show that the beta-chains repertoire size of the CD4 memory compartment is only two times smaller, and that of the CD8 memory compartment is only 3-10 times smaller than the naive compartments. Our results show that the T-cell memory compartment has a very different distribution of clones than anticipated. This has important implications for the current dogma of immunological memory, and changes the interpretation of repertoire aberrations in (patho-)physiological situations such as ageing and auto-immunity. It raises new questions on the factors that steer maturation of memory phenotype and determine the size of memory clones. (C) 2010 Elsevier B.V. All rights reserved.