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CD4+ T cells persist for years in the human small intestine and mediate robust Th1 immunity.

Bartolome Casado, R.; Landsverk, O. J. B.; Kumar Chauhan, S.; Saetre, F.; Hagen, K. T.; Yaqub, S.; Oyen, O.; Horneland, R.; Aandahl, E. M.; Aabakken, L.; Baekkevold, E. S.; Jahnsen, F. L.

2019-12-03 immunology
10.1101/863407 bioRxiv
Show abstract

Studies in mice and humans have shown that CD8+ T cell immunosurveillance in non-lymphoid tissues is dominated by resident populations. Whether CD4+ T cells use the same strategies to survey peripheral tissues is less clear. Here, examining the turnover of CD4+ T cells in transplanted duodenum in humans, we demonstrate that the majority of CD4+ T cells were still donor-derived one year after transplantation. In contrast to memory CD4+ T cells in peripheral blood, intestinal CD4+ TRM cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4+ TRM cells were very potent cytokine producers; the vast majority being polyfunctional TH1 cells, whereas a minor fraction produced IL-17. Interestingly, a fraction of intestinal CD4+ T cells produced granzyme-B and perforin after activation. Together, we show that the intestinal CD4+ T-cell compartment is dominated by resident populations that survive for more than 1 year. This finding is of high relevance for the development of oral vaccines and therapies for diseases in the gut.

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