As depicted in Fig. 8(a), cell–cell contact between CD4+ responder T cells and TGF-β/RA-induced CD8+ Foxp3+/GFP+ T cells is mandatory for the regulatory function of these cells. As a result of the cell–cell contact-dependency of TGF-β/RA-induced Selleck MLN0128 CD8+ Foxp3+/GFP+ T cells and the fact that modulation of antigen-presenting cells (APC) is one of several postulated mechanism of CD4+ regulatory T-cell-mediated suppression we further investigated the role of DCs in a T-cell suppression assay. Therefore, we performed inhibition assays with and without the presence of DCs. Interestingly, the

suppressive activity of TGF-β/RA-induced CD8+ Foxp3+/GFP+ T cells is only detectable in the presence of DCs (Fig. 8b). This finding suggests that TGF-β/RA-induced CD8+ Foxp3+/GFP+ T cells exert their suppressive function by modulating the stimulatory function of DCs. The intestinal immune system is constantly challenged by foreign antigens and commensal bacteria. Therefore, proper control of the intestinal microenvironment is required. One important arm of this regulatory network consists of regulatory T cells. Many researchers have undertaken association studies among patients with IBD to determine whether changes in regulatory T cells can be correlated with disease severity, with a particular focus

on defining the differences between circulating cells and cells from gut tissue. Most of these studies have analysed CD4+ CD25+ Foxp3+ selleck chemicals regulatory T cells, and much less is known about the role of CD8+ regulatory T cells in IBD. Mayer and colleagues suggested that a defect of CD8+ regulatory T cells in the LP may lead to the development of IBD.14,15 These researchers demonstrated that CD8+ T cells isolated from non-inflamed mucosa display suppressive Fenbendazole capabilities; in contrast, LP CD8+ T cells derived from patients with IBD could not suppress immune responses. They conclude that CD8+ T cells with regulatory activity are present in

the LP of normal healthy persons but not in the LP of patients with IBD. In the present study we demonstrated that the peripheral blood of patients with UC contains fewer CD8+ CD25+ Foxp3+ T cells when the disease is active. These findings are in line with those of earlier studies, which demonstrated that the peripheral blood of patients with Crohn’s disease and UC contains fewer CD4+ regulatory T cells during disease flares, and suggest that the severity of disease is inversely correlated with the number of regulatory T cells in the peripheral blood.22–24 Despite our limited understanding of the role of regulatory T cells in the pathogenesis of human IBD, the ability to alter regulatory pathways may be a crucial avenue for achieving long-term remission. Results from animal models suggest that the transfer of regulatory T cells may be beneficial.