title: Transforming growth factor-β protein inversely regulates in vivo differentiation of interleukin-17 (IL-17)-producing CD4+ and CD8+ T cells.
abstract: TGF-β is a pleiotropic cytokine that predominantly exerts inhibitory functions in the immune system. Unexpectedly, the in vitro differentiation of both Th17 and Tc17 cells requires TGF-β. However, animals that are impaired in TGF-β signaling (TGF-βRIIDN mice) display multiorgan autoimmune disorders. Here we show that CD4(+) T cells from TGF-βRIIDN mice are resistant to Th17 cell differentiation and, paradoxically, that CD8(+) T cells from these animals spontaneously acquire an IL-17-producing phenotype. Neutralization of IL-17 or depletion of CD8(+) T cells dramatically inhibited inflammation in TGF-βRIIDN mice. Therefore, the absence of TGF-β triggers spontaneous differentiation of IL-17-producing CD8(+) T cells, suggesting that the in vivo and in vitro conditions that promote the differentiation of IL-17-producing CD8(+) T cells are distinct.
authors.affiliation: Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Ved Prakash
authors.initials: VP
authors.lastname: Dwivedi
authors.forename: Sultan
authors.initials: S
authors.lastname: Tousif
authors.forename: Debapriya
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Durbaka Vijay Raghva
authors.initials: DV
authors.lastname: Prasad
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Jyoti
authors.initials: J
authors.lastname: Das
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta