CD4+CD25+ T cells regulate colonic localization of CD4 T cells reactive to a microbial antigen.

Abstract

BACKGROUND: In patients with inflammatory bowel diseases, T-cell activation driven by microflora has been implicated as a mechanism causing clonal expansion and infiltration of CD4+ T cells in colonic lamina propria (LP). We explored a regulatory mechanism preventing infiltration of CD4+ T cells specific to a microbe-associated antigen in the gut. METHODS: SCID mice were reconstituted with CD4+ T cells specific to ovalbumin (OVA) and were orally administered with Escherichia coli engineered to produce OVA. RESULTS: OVA-specific CD4+ T cells (KJ1-26+) were recruited to colonic LP in an Ag-dependent manner, which was inhibited by adoptive transfer of naturally occurring CD4+CD25+ T (Treg) cells. KJ1-26+ T cells and Treg cells are localized preferentially to the colonic follicles that contain dendritic cells. In mice given Treg cells, LP CD4+ T cells showed a decrease in proliferative and interferon gamma response and an increase in transforming growth factor beta1 response to OVA stimulation. Treg cells inhibited both antigenic activation of effector CD4+ T cells and class II/CD80/CD86 up-regulation of dendritic cells. CONCLUSION: : Treg cells suppress recruitment of CD4+ T cells specific to a microbe-associated antigen to LP, which was associated with colocalization of effector CD4+ T cells and Treg cells in colonic follicles.