Peripheral differentiation patterns of human T cells

Funding Information: We thank the nurses of the Transplantation Unit of Helsinki University Central Hospital, HiLife Flow Cytometry Unit of University of Helsinki, and Tamás Bazsinka for technical support. This study has been funded by Emil Aaltonen Foundation, Finnish Medical Foundation, Foundation for Pediatric Research, Biomedicum Helsinki Foundation, Roche Research grant, the MD PhD program of the University of Helsinki, and the Competitive State Research Financing of Responsibility Area of Helsinki University Hospital (TYH2019307). Publisher Copyright: © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. Long-term T-cell memory is dependent on the maintenance of memory T cells in the lymphoid tissues, and at the surface interfaces that provide entry routes for pathogens. However, much of the current information on human T-cell memory is based on analyzing circulating T cells. Here, we have studied the distribution and age-related changes of memory T-cell subsets in samples from blood, mesenteric LNs, spleen, and ileum, obtained from donors ranging in age from 5 days to 67 years of age. Our data show that the main reservoir of polyclonal naive cells is found in the LNs, and the resting memory subsets capable of self-renewal are also prominent there. In contrast, nondividing but functionally active memory subsets dominate the spleen, and especially the ileum. In general, the replacement of naive cells with memory subsets continues throughout our period of observation, with no apparent plateau. In conclusion, the analysis of lymphoid and nonlymphoid tissues reveals a dynamic pattern of changes distinct to each tissue, and with substantial differences between CD4+ and CD8+ compartments.