<i>Lactobacillus reuteri</i> induces gut intraepithelial CD4⁺CD8αα⁺ T cells.

Abstract

The small intestine contains CD4⁺CD8αα⁺ double-positive intraepithelial lymphocytes (DP IELs), which originate from intestinal CD4⁺ T cells through down-regulation of the transcription factor Thpok and have regulatory functions. DP IELs are absent in germ-free mice, which suggests that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of <i>Lactobacillus reuteri</i> This species induced DP IELs in germ-free mice and conventionally-raised mice lacking these cells. <i>L. reuteri</i> did not shape the DP-IEL-TCR (TCR, T cell receptor) repertoire but generated indole derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4⁺ T cells, allowing Thpok down-regulation and differentiation into DP IELs. Thus, <i>L. reuteri</i>, together with a tryptophan-rich diet, can reprogram intraepithelial CD4⁺ T cells into immunoregulatory T cells.