T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease

T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-bet(−/−) mice and was associated with low IFN-γ production and elevated IL-17 production among central nervous system (CNS) infiltrating CD4(+) T cells. T-bet(−/−) Th17 cells generated in the presence of IL-6/TGF-β/IL-1 and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon transfer to naïve mice. Unlike their WT counterparts, these T-bet(−/–) Th17 cells did not exhibit an IL-17→IFN-γ switch upon reencounter with antigen in the CNS, indicating that this functional change is not critical to disease development. In contrast, T-bet was absolutely required for the pathogenicity of myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation.