title: CD4+ Foxp3+ regulatory T cells suppress γδ T-cell effector functions in a model of T-cell-induced mucosal inflammation.
abstract: 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 αβ T-cell-deficient (TCR-β(-/-) ) 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 γδ 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 γδ T-cell expansion and cytokine production in vitro and in vivo, suggesting a pathogenic role of γδ T cells in intestinal inflammation. Thus, functional alterations in T(REG)  cells provoke dysregulated CD4(+)  and γδ T-cell responses to commensal antigens in the intestine.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Yurchenko
authors.forename: Megan K
authors.initials: MK
authors.lastname: Levings
authors.forename: Ciriaco A
authors.initials: CA
authors.lastname: Piccirillo
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma