The interaction of intestinal epithelial cells and intraepithelial lymphocytes in host defense.
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-CD8alphaalpha+ T cells expressing T cell receptor (TCR)alphabeta or TCRgammadelta and CD4+ CD8alphaalpha+ T cells expressing TCR alphabeta. We show here that CD4+ CD8alphaalpha+ 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/alphaEbeta7 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 of L. monocytogenes into i-EC activated NFkappa-B and subsequently up-regulated the expression of IL-15 gene, which has a NFkappa-B binding site at the promoter region. i-IEL, especially gammadelta T cells, were significantly activated to produce Th1 type cytokines at the early stage after oral infection with L. 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.
Yoshikai
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Y
Laboratory of Host Defense, Research Institute for Disease for Mechanism and Control, Nagoya University School of Medicine, Japan. yoshika@med.nagoya-u.ac.jp
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015820:Cadherins / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007111:Immunity, Cellular; D016023:Integrins / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D008089:Listeria monocytogenes / Q000378:metabolism / Q000472:pathogenicity; D008285:Major Histocompatibility Complex / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D015820:Cadherins; D016023:Integrins; D019409:Interleukin-15; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor