MyD88-dependent signaling for IL-15 production plays an important role in maintenance of CD8αα TCRαβ and TCRγδ intestinal intraepithelial lymphocytes

Interaction between commensal bacteria and intestinal epithelial cells (i-ECs) via TLRs is important for intestinal homeostasis. In this study, we found that the numbers of CD8 alpha alpha TCR alpha beta and TCR gamma delta intestinal intraepithelial lymphocytes (MELs) were significantly decreased in MyD88-deficient (-/-) mice. The expression of IL-15 by i-ECs was severely reduced in MyD88(-/-) mice. Introduction of IL-15 transgene into MyD88(-/-) mice (MyD88(-/-) IL-15 transgenic mice) partly restored the numbers of CD8 alpha alpha TCR alpha beta and TCR gamma delta i-IELs. The i-IEL in irradiated wild-type (WT) mice transferred with MyD88(-/-) bone marrow (BM) cells had the same proportions of i-IEL as WT mice, whereas those in irradiated MyD88(-/-) mice transferred with WT BM cells showed significantly reduced proportions of CD8 alpha alpha TCR alpha beta and TCR gamma delta i-IELs, as was similar to the proportions found in MyD88-'mice. However, irradiated MyD88(-/-) IL-15 transgenic mice transferred with WT BM cells had increased numbers of CD8 alpha alpha TCR alpha beta and TCR gamma delta subsets in the i-IEL. These results suggest that parenchymal cells such as i-ECs contribute to the maintenance of CD8 alpha alpha TCR alpha beta and gamma delta i-IELs at least partly via MyD88-dependent IL-15 production.