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

FOXP3⁺CD4⁺ regulatory T cells (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⁺ T_R in Crohn's disease (CD). We report that FOXP3⁺CD4⁺ T_R 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-α inhibitors, have a lower frequency of PB FOXP3⁺CD4⁺ 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^- T cells. T cell 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-β. In summary, there is an expansion of FOXP3⁺CD4⁺ T_R cells in mucosal lymphoid tissues in CD; they accumulate in areas of active inflammation, including granulomas and retain potent regulatory activity ex vivo.