CD4 T cells persist for years in the human small intestine and display a T1 cytokine profile.

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 T cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4 T cells were very potent cytokine producers; the vast majority being polyfunctional T1 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.