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MyD88-Dependent Signaling for IL-15 Production Plays an Important Role in Maintenance of CD8 TCR and TCR Intestinal Intraepithelial Lymphocytes¹

Qingsheng Yu^*, Ce Tang^*, Sun Xun^*, Toshiki Yajima^*, Kiyoshi Takeda and Yasunobu Yoshikai^2,*

^* Division of Host Defense and Division of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

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 TCR and TCR intestinal intraepithelial lymphocytes (i-IELs) 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 TCR and TCR 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 TCR and TCR 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 TCR and TCR subsets in the i-IEL. These results suggest that parenchymal cells such as i-ECs contribute to the maintenance of CD8 TCR and i-IELs at least partly via MyD88-dependent IL-15 production.

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