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The interaction of intestinal epithelial cells and intraepithelial lymphocytes in host defense

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Abstract

Intestinal intraepithelial lymphocytes (i-IEL) are located at the basolateral surfaces of intestinal epithelial cells (i-EC) and play important roles in the homeostasis of intestinal microenvironment. i-IEL comprise unique T cell populations including CD4-CD8αα+ T cells expressing T cell receptor (TCR)αΒ or TCRγδ and CD4+ CD8αα+ T cells expressing TCR αΒ. We show here that CD4+ CD8αα+ i-IEL belongs to Th1 type T cells capable of responding to self-MHC class I on i-EC and that a significant fraction of i-IEL expressed Fas ligand (Fas-L) and induced apoptosis in the i-EC via Fas-dependent pathway. i-IEL may recognize and eliminate the effete i-EC for homeostatic regulation of intestinal epithelia. The interaction of i-EC and i-IEL through E-cadherin/αEΒ7 integrin is important for homing and maintenance of i-IEL in intestine.Listeria monocytogenes are also known to interact with E-cadherin on i-EC and invade into the epithelial cells. Invasion ofL. monocytogenes into i-EC activated NFk-B and subsequently up-regulated the expression of IL-15 gene, which has a NFk-B binding site at the promoter region. i-IEL, especially γδ T cells, were significantly activated to produce Th1 type cytokines at the early stage after oral infection withL. monocytogenes in mice and rats. The activation of i-IEL coincided with a peak response of IL-15 production by i-EC after infection. Taken together, mutual interaction of i-IEL and i-EC may be important not only for homeostatic regulation but also host defense against microbial infection in intestine.

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Correspondence to Yasunobu Yoshikai MD, PhD.

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Yoshikai, Y. The interaction of intestinal epithelial cells and intraepithelial lymphocytes in host defense. Immunol Res 20, 219–235 (1999). https://doi.org/10.1007/BF02790405

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