Enteric bacterial antigens activate CD4(+) T cells from scid mice with inflammatory bowel disease

Scid mice transplanted with CD4(+) T cells from congenic donor mice develop a chronic and lethal inflammatory bowel disease (IBD) 2-3 months post-tran splantation. In the present study we have investigated the response of CD4( +) T cells from sold mice with colitis against fecal extracts. Our results show that in contrast to CD4(+) T cells from normal BALB/c mice, CD4(+) T c ells from scid mice with colitis proliferate strongly in response to antige n-presenting cells (APC) pulsed with fecal extracts. The IBD-associated T c ells did not respond to either extracts from food antigens or fecal extract s from germ-free mice, which indicates that they recognize bacterial antige ns in the fecal extracts. CD4(+) T cells isolated from the colonic lamina p ropria of scid mice 3 weeks post transplantation also responded vigorously to fecal extracts, demonstrating that reactive CD4(+) T cells are present i n the gut mucosa of transplanted scid mice prior to clinical manifestations of IBD. CD4(+) T cells activated by fecal extracts produced high amounts o f IL-2 and IFN-gamma, intermediate amounts of IL-4 and low amounts of IL-10 , consistent with a Th1 profile. The proliferative reactivity towards fecal extracts was restricted by MHC class II molecules and dependent on antigen processing, as the response could be blocked by anti-MHC class II antibodi es or a short fixation of the APC. This study demonstrates that class II-re stricted CD4(+) Th1 cells, which recognize enteric bacterial antigens, infi ltrate the gut mucosa and spleen of transplanted sold mice prior to and dur ing the course of colitis.