Long-term maintenance of human naïve T cells through in situ homeostasis in lymphoid tissue sites

JJC Thome, B Grinshpun, BV Kumar, M Kubota… - Science …, 2016 - science.org
JJC Thome, B Grinshpun, BV Kumar, M Kubota, Y Ohmura, H Lerner, GD Sempowski…
Science immunology, 2016science.org
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 …
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.
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