1E), suggesting a dysregulated expansion of donor TEFF cells in the absence of TREG cells. In order to examine kinetics of lymphocyte proliferation in TCR-β−/− recipient mice, cycling cells from secondary lymphoid tissues and LP were determined by intracellular Ki-67 expression at different time points during disease progression. Our results show a progressive

increase in frequencies and selleckchem absolute numbers of cycling lymphocytes in colitic mice (Fig. 1F), which was significantly decreased in all lymphoid organs examined, as well as in the LP, upon TREG-cell co-transfer (Fig. 1F and G). More importantly, the reduced absolute numbers of donor TEFF cells in mesLN compared with LP (Fig. 1G) suggests that TREG cells hamper the expansion and accumulation of pathogenic cells in the site of Idasanutlin research buy tissue inflammation. Studies show that a prominent role for Th1, and in particular Th17, polarized immune responses in autoimmunity and IBD-like disorders in humans and in mouse models 44, 45. In particular,

IL-17-secreting T cells are found in lesions of patients with CD 4, 22, 25, and genome-wide association studies of CD and ulcerative colitis patients indicate the importance of Th17-promoting factors, including IL-23, in IBD 46, 47. We then sought to characterize the inflammatory nature of the mucosal inflammation. We observed a significant increase in IFN-γ IL-1β, IL-12 and IL-6 mRNA expression in colons of mice reconstituted with

CD4+CD25− TEFF cells alone, while CD4+CD25+ TREG cell-mediated protection from colitis correlated with higher levels of IL-4 and IL-10 mRNA expression (Fig. 2A). Moreover, we found a marked increase in frequencies and absolute numbers of IFN-γ- and IL-17-producing lymphocytes in secondary lymphoid tissues and LP of colitic mice (Fig. 2B–E), indicating that TREG cells potently Montelukast Sodium suppress the priming and expansion of these cells in protected mice. Interestingly, our results reveal a temporal difference in the emergence of IFN-γ- and IL-17-producing cells. While IFN-γ was highly expressed in the absence of TREG cells in both perLN and mesLN (Fig. 2B), IL-17 secretion was more specific to the intestinal tissue (Fig. 2B and C). This is consistent with previous studies pointing to the mucosa as a privileged site for Th17-cell development due to elevated secretion of specific polarizing mediators such as IL-6 and TGF-β1 25. Moreover, while the frequency of IFN-γ-secreting CD4+ TEFF cells (≈40% of CD4+ T cells) in the inflammatory site remained unchanged during colitis development, the frequency of IL-17+ donor CD4+ TEFF cells steadily dropped from 35% at day 7 to 20% at day 21 (Fig. 2D and E), suggesting a role for different signals in the initial and progressive phases of T-cell-induced colitis in TCR-β−/− mice.