A mucosal intranet: intestinal epithelial cells down-regulate intraepithelial, but not peripheral, T lymphocytes.
Epithelial cells and lymphocytes, including gammadelta and alphabeta T cells, in the gastrointestinal tract epithelium represent a major host defense intranet that is incompletely understood. Cell-to-cell interactions between intraepithelial lymphocytes (IELs) and intestinal epithelial cells (IECs) comprise this intranet, and we have assessed the role of IECs in the regulation of gammadelta and alphabeta T cell responses. When highly purified CD3+ IEL T cells were stimulated via the TCR-CD3 complex, high proliferative responses and cytokine synthesis were induced. However, the addition of viable IECs or purified IEC membranes (mIEC) down-regulated T cell proliferative and cytokine responses. Further, the inhibitory effect of mIEC was not restored by antibodies to TGF-beta, CD1d, E-cadherin, or MHC class I or II. This inhibitory effect was noted for both gammadelta and alphabeta T cell subsets from IELs, and mRNA levels were reduced for both Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-5) cytokines in gammadelta and alphabeta IELs. In contrast, a purified membrane fraction obtained from thymocytes did not inhibit IEL proliferative responses. Further, mIEC did not inhibit splenic alphabeta T cell proliferative responses. These findings show that cell-to-cell interactions between intraepithelial gammadelta and alphabeta T cells and IECs occur via cell surface molecules, suggesting an intranet to prevent potential inflammatory responses at the intestinal mucosal surface.
Yamamoto
M
M
Immunobiology Vaccine Center, Department of Oral Biology, University of Alabama Medical Center, Birmingham 35294, USA.
Fujihashi
K
K
Kawabata
K
K
McGhee
J R
JR
Kiyono
H
H
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018949:Antigens, CD1 / Q000276:immunology; D015820:Cadherins / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D015820:Cadherins; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta