期刊
SCIENCE IMMUNOLOGY
卷 1, 期 6, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aah6506
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资金
- NIH [AI106697, AI100119, F31AG047003]
- BD Bioscience Research Grant
- Adaptive Biosciences Young Investigator Award
- CCTI Flow Cytometry Core [S10RR027050]
Naive T cells develop in the thymus and coordinate immune responses to new antigens; however, mechanisms for their long-term persistence over the human life span remain undefined. We investigated human naive T cell development and maintenance in primary and secondary lymphoid tissues obtained from individual organ donors aged 2 months to 73 years. In the thymus, the frequency of double-positive thymocytes declined sharply in donors >40 years of age, coincident with reduced recent thymic emigrants in lymphoid tissues, whereas naive T cells were functionally maintained predominantly in lymph nodes (LNs). Analysis of T cell receptor clonal distribution by CDR3 sequencing of naive CD4(+) and CD8(+) T cells in spleen and LNs reveals site-specific clonal expansions of naive T cells from individuals >40 years of age, with minimal clonal overlap between lymphoid tissues. We also identified biased naive T cell clonal distribution within specific LNs on the basis of VJ usage. Together, these results suggest prolonged maintenance of naive T cells through in situ homeostasis and retention in lymphoid tissue.
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