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

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 beta 1 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.