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-transplantation. In the present study we have investigated the response of CD4(+) T cells from scid mice with colitis against fecal extracts. Our results show that in contrast to CD4(+) T cells from normal BALB/c mice, CD4(+) T cells from scid mice with colitis proliferate strongly in response to antigen-presenting cells (APC) pulsed with fecal extracts. The IBD-associated T cells did not respond to either extracts from food antigens or fecal extracts from germ-free mice, which indicates that they recognize bacterial antigens in the fecal extracts. CD4(+) T cells isolated from the colonic lamina propria of scid mice 3 weeks post transplantation also responded vigorously to fecal extracts, demonstrating that reactive CD4(+) T cells are present in the gut mucosa of transplanted scid mice prior to clinical manifestations of IBD. CD4(+) T cells activated by fecal extracts produced high amounts of 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 antibodies or a short fixation of the APC. This study demonstrates that class II-restricted CD4(+) Th1 cells, which recognize enteric bacterial antigens, infiltrate the gut mucosa and spleen of transplanted scid mice prior to and during the course of colitis.
Brimnes
J
J
Department of Medical Anatomy A, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Reimann
J
J
Nissen
M
M
Claesson
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005856:Germ-Free Life; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007422:Intestines / Q000382:microbiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology
D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007371:Interferon-gamma