Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine.
T cells in explants of human fetal small intestine in organ culture were stimulated in situ with PWM or anti-CD3 antibody to test the hypothesis that activated T cells produce enteropathy in human small intestine. T cell activation was measured by the appearance of CD25+ cells in the lamina propria of the explants and IL-2 production into the organ culture supernatant. We have previously shown that the number of T cells in human fetal gut increased between 14 and 22 wk gestation. Accordingly, after the addition of PWM to cultured explants of fetal intestine the number of CD25+ cells in the lamina propria and the amounts of IL-2 secreted into the organ culture supernatant increased with the age of the explanted tissue. The addition of PWM also produced an age-related enteropathy, most noticeably crypt epithelial cell hyperplasia and villous atrophy, with relatively minor changes in 14-17-wk-old intestine but severe tissue damage in 18-22-wk-old fetal intestine. These enteropathic effects were also produced when mucosal T cells were activated with anti-CD3 mAb. Cyclosporin A completely inhibited the PWM-induced development of CD25+ cells and related tissue damage. These experiments show that activated T cells in human small intestine produce enteropathy. The model provides a new system with which to dissect the mechanisms of T cell-mediated intestinal damage.
MacDonald
T T
TT
Department of Paediatric Gastroenterology, St. Bartholomews Hospital, London, United Kingdom.
Spencer
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D003524:Cyclosporins / Q000494:pharmacology; D004751:Enteritis / Q000209:etiology; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D007421:Intestine, Small / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D009924:Organ Culture Techniques; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D007376:Interleukin-2; D011043:Pokeweed Mitogens