Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease

FOXP3(+)CD4(+) regulatory Tcells (T-R) have emerged as important regulators of immune responses. The aim of our study was to assess the frequency and functional characteristics of FOXP3+CD4+ TR in Crohn's disease (CD). We report that FOXP3(+)CD4(+) TR cells are expanded in mucosal lymphoid tissues (lamina propria and MLN) but are decreased in the PB in active CD. Patients treated with thiopurines, but not steroids or anti-TNF-alpha inhibitors, have a tower frequency of PB FOXP3(+)D4(+)T(R) (7.8 +/- 2.4% vs. 9.9 +/- 1.8%, p=0.01). FOXP3(+) cells were localized in the lamina propria (LP), muscularis mucosa and serosa and accumulated in granulomas, whereas in MLN they localize in the T cell rich areas. MLN CD4'CD25+ T cells from both CD and normal intestine efficiently suppress the proliferation of effector CD4(+)CD25(-) Tcells. Tcell activation of MLN in vitro with anti-CD3 plus anti-CD28 Abs enhances the expression of FOXP3, both at the protein and transcriptional level, which is further enhanced by the addition of TGF-beta. In summary, there is an expansion of FOXP3(+)CD4(+) TR cells in mucosal Lymphoid tissues in CD; they accumulate in areas of active inflammation, including granulomas and retain potent regulatory activity ex vivo. (c) 2007 Elsevier Inc. All rights reserved.