Characterization of immunomodulatory properties and accessory cell function of small intestinal epithelial cells.
We have studied the immunomodulatory properties of epithelial cells from the small intestine on T cell immune function in vitro. Proliferation of lymph node cells stimulated either with antigen or with mitogen was inhibited by epithelial cells in a dose-dependent fashion. The epithelial cell-mediated suppression of lymphocyte proliferation was blocked by indomethacin, a cyclooxygenase pathway inhibitor, demonstrating that the suppressive effect of epithelial cells was related to prostaglandin secretion. Furthermore, the action of epithelial cell-secreted prostaglandin on lymphocytes was related to its effect on IL-2 as the suppressive effect of epithelial cells was abrogated by the addition of exogenous IL-2. As previously reported, epithelial cells constitutively express MHC class II and we found them able to present antigen in a class II-restricted fashion when their suppressive effects were blocked by indomethacin. Furthermore, epithelial cells activated by LPS secrete an IL-1 like molecule in a fashion analogous to other antigen-presenting cells. These results demonstrate that epithelial cells can both enhance and suppress in vitro T cell immune responses and further characterize the mechanisms by which intestinal epithelial cells may function in gut-associated immune responses.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
L M
LM
Santos
O
O
Lider
J
J
Audette
S J
SJ
Khoury
H L
HL
Weiner
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005260:Female; D007165:Immunosuppression Therapy; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D004676:Myelin Basic Protein / Q000276:immunology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D007375:Interleukin-1; D007376:Interleukin-2; D004676:Myelin Basic Protein; D011453:Prostaglandins; D007213:Indomethacin