CD4+T cells persist for years in the human small intestine and display a TH1 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(RM)cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4(+)T(RM)cells were very potent cytokine producers; the vast majority being polyfunctional T(H)1 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.

Automated summary

Studies have shown that the majority of CD4(+)T cells in the transplanted duodenum remain donor-derived resident cells after one year, with a strong cytokine-producing capability mainly as polyfunctional T(H)1 cells. This finding is important for the development of oral vaccines and therapies for gut diseases.