Role of the microbiota in the development of intraepithelial CD4+CD8aa+ T cells

Abstract The small intestine contains CD4+CD8aa+ double-positive intraepithelial T lymphocytes (DP IELs) which originate from intestinal CD4+ T cells through downregulation of the transcription factor ThpoK and have regulatory functions. We have previously found that development of DP IEL depend on the presence of Lactobacillus reuteri. This species induced DP IELs in germ-free mice and conventionally-raised mice lacking these cells. L. reuteri did not shape DP-IEL-TCR repertoire, but generated indol derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4+ T cells. Monocolonization of germ-free mice with L. reuteri resulted in the induction of DP IEL, however reconstitution with a complex microbiota + L. reuteri induce a much larger DP IEL population suggesting that additional bacterial species are required for optimal DP IEL development. In this study we have aimed at elucidating additional bacterial species from the intestinal microbiota that contribute to the development of DP IEL.