Thome Joseph J C, Grinshpun Boris, Kumar Brahma V, Kubota Masa, Ohmura Yoshiaki, Lerner Harvey, Sempowski Gregory D, Shen Yufeng, Farber Donna L
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
Sci Immunol. 2016 Dec;1(6). doi: 10.1126/sciimmunol.aah6506. Epub 2016 Dec 2.
Naïve T cells develop in the thymus and coordinate immune responses to new antigens; however, mechanisms for their long-term persistence over the human lifespan remain undefined. Here, we investigated human naïve T cell development and maintenance in primary and secondary lymphoid tissues obtained from individual organ donors aged 3 months-73 years. In the thymus, the frequency of double-positive thymocytes declined sharply in donors over age 40 coincident with reduced recent thymic emigrants (RTE) in lymphoid tissues, while naïve T cells were functionally maintained predominantly in lymph nodes (LN). Analysis of TCR clonal distribution by CDR3 sequencing of naïve CD4 and CD8 T cells in spleen and LNs reveal site-specific clonal expansions of naïve T cells from individuals >40 years of age with minimal clonal overlap between lymphoid tissues. We also identified biased naïve T cell clonal distribution within specific lymph nodes based on VJ usage. Together these results suggest prolonged maintenance of naïve T cells through homeostasis and retention in lymphoid tissue.
初始T细胞在胸腺中发育，并协调对新抗原的免疫反应；然而，它们在人类生命周期中长期持续存在的机制仍不明确。在此，我们研究了从3个月至73岁个体器官捐赠者获取的初级和次级淋巴组织中人类初始T细胞的发育和维持情况。在胸腺中，40岁以上捐赠者的双阳性胸腺细胞频率急剧下降，同时淋巴组织中近期胸腺迁出细胞（RTE）减少，而初始T细胞主要在功能上维持于淋巴结（LN）中。通过对脾脏和淋巴结中初始CD4和CD8 T细胞进行CDR3测序分析TCR克隆分布，发现40岁以上个体的初始T细胞存在位点特异性克隆扩增，且淋巴组织之间的克隆重叠极少。我们还基于VJ使用情况确定了特定淋巴结内初始T细胞的偏向性克隆分布。这些结果共同表明，初始T细胞通过内稳态和在淋巴组织中的留存得以长期维持。
