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- Title
Long-term maintenance of human naïve T cells through in situ homeostasis in lymphoid tissue sites.
- Authors
Thome, Joseph J. C.; Grinshpun, Boris; Kumar, Brahma V.; Masaru Kubota; Yoshiaki Ohmura; Lerner, Harvey; Sempowski, Gregory D.; Yufeng Shen; Farber, Donna L.
- Abstract
Naïve 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 naïve 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 naïve T cells were functionally maintained predominantly in lymph nodes (LNs). Analysis of T cell receptor clonal distribution by CDR3 sequencing of naïve CD4+ and CD8+ T cells in spleen and LNs reveals 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 LNs on the basis of VJ usage. Together, these results suggest prolonged maintenance of naïve T cells through in situ homeostasis and retention in lymphoid tissue.
- Subjects
T cells; LYMPHOID tissue; THYMUS; IMMUNE response; THYMOCYTES
- Publication
Science Immunology, 2016, Vol 1, Issue 6, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.aah6506