Human lymph nodes maintain a distinct subset of TCF-1hi resident memory T cells with stem-like properties throughout life. Homo sapiens

Tissue resident memory T cells (TRM) predominate in barrier sites and mediate protective immunity, while their role in lymphoid tissues is undefined. Here we analyzed memory CD8+ T cells in different lymphoid compartments including bone marrow, spleen, and lymph nodes (LN) relative to lung within diverse individuals. We identify an organ-specific subset in human LN (TLN) not found in blood or other tissues, expressing high levels of TCF-1 and transcriptionally enriched for markers of quiescence, self-renewal and follicular-helper cells. High dimensional CyTOF analysis reveals TLN as intermediate in differentiation between naive and TRM cells, with circulating memory T cells the most differentiated. TLN exhibit higher TCR diversity, lower in vivo turnover, yet higher proliferative responses compared to memory cells in otherlymphoid or mucosal sites. These findings establish human LN as reservoirs for diverse memory T cells poised for high expansion and TLN as important targets for in vivo immunotherapies.