RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.
Long-term maintenance of human naïve T cells through in situ homeostasis in lymphoid tissue sites
Thome, J. J. C., Grinshpun, B., Kumar, B. V., Kubota, M., Ohmura, Y., Lerner, H., Sempowski, G. D., Shen, Y., & Farber, D. L. (2016). Long-term maintenance of human naïve T cells through in situ homeostasis in lymphoid tissue sites. Science immunology, 1(6). https://doi.org/10.1126/sciimmunol.aah6506
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 in situ homeostasis and retention in lymphoid tissue.
