| First Author | Yurchenko E | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 12 | Pages | 3455-66 |
| PubMed ID | 21956668 | Mgi Jnum | J:179507 |
| Mgi Id | MGI:5302589 | Doi | 10.1002/eji.201141814 |
| Citation | Yurchenko E, et al. (2011) CD4+ Foxp3+ regulatory T cells suppress gammadelta T-cell effector functions in a model of T-cell-induced mucosal inflammation. Eur J Immunol 41(12):3455-66 |
| abstractText | CD4(+) CD25(+) Foxp3(+) regulatory T (T(REG) ) cells are critical mediators of peripheral immune tolerance, and abrogation of their function provokes a variety of autoimmune and inflammatory states including inflammatory bowel disease. In this study, we investigate the functional dynamics of T(REG) -cell responses in a CD4(+) T-cell-induced model of intestinal inflammation in alphabeta T-cell-deficient (TCR-beta(-/-) ) hosts to gain insights into the mechanism and cellular targets of suppression in vivo. We show that CD4(+) T effector cell transfer into T-cell-deficient mice rapidly induces mucosal inflammation and colitis development, which is associated with prominent Th1 and Th17 responses. Interestingly, we unveil a prominent role for resident gammadelta T cells in mucosal inflammation as they promote Th1 and particularly Th17 responses in the early phase of inflammation, thus exacerbating colitis development. We further demonstrate that CD4(+) CD25(+) Foxp3(+) T(REG) cells readily inhibit these responses and mediate disease protection, which correlates with their accumulation in the draining LN and lamina propria. Moreover, T(REG) cells can directly suppress gammadelta T-cell expansion and cytokine production in vitro and in vivo, suggesting a pathogenic role of gammadelta T cells in intestinal inflammation. Thus, functional alterations in T(REG) cells provoke dysregulated CD4(+) and gammadelta T-cell responses to commensal antigens in the intestine. |
