Cutting Edge: The Pathogenicity of IFN-γ–Producing Th17 Cells Is Independent of T-bet

摘要

During the development of experimental autoimmune encephalomyelitis (EAE), the proportion of pathogenic and myelin-specific cells within CNS-infiltrating cytokine-producing Th cells is unknown. Using an IL-17A/IFN-γ double reporter mouse and I-Ab/myelin oligodendrocyte glycoprotein 38–49 tetramer, we show in this study that IL-17+IFN-γ+ Th cells, which are expanded in the CNS during EAE, are highly enriched in myelin oligodendrocyte glycoprotein–specific T cells. We further demonstrate that IL-23 is essential for the generation and expansion of IFN-γ–producing Th17 cells independently of the Th1-associated transcription factors T-bet, STAT1, and STAT4. Furthermore, Th17 and IL-17+IFN-γ+ Th cells can induce CNS autoimmunity independently of T-bet. Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell–mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-γ expression in Th1 and Th17 cells.