CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis.
Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10 and TGF-beta, and is not prevented by the addition of high doses of IL-2 to the assay culture. Functionally and phenotypically the T-reg cells of the present study differ from previously described subsets of T-reg cells. The presence of T cells with a regulatory potential in the normal colonic mucosa suggests a role for these cells in the maintenance of local immune homeostasis of the gut.
Gad
M
M
Department of Medical Anatomy A, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Brimnes
J
J
Claesson
M H
MH
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D002455:Cell Division; D003106:Colon / Q000382:microbiology; D004755:Enterobacteriaceae; D004756:Enterobacteriaceae Infections / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D018417:Th1 Cells / Q000473:pathology*
D000942:Antigens, Bacterial