T‐bet is essential for the progression of experimental autoimmune encephalomyelitis

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Abstract
Summary: Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin‐specific CD4+ T helper 1 (Th1) cells, while recovery from the disease is associated with the presence of Th2 cells. Here we used animals with targeted deletion of the T‐bet gene to determine its role in the progression of EAE. T‐bet regulates the production of interferon‐γ (IFN‐γ) in CD4+ and natural killer cells, and CD4+ T cells from T‐bet‐deficient mice were unable to differentiate into a Th1 phenotype. Moreover BALB/c mice deficient in T‐bet were resistant to the induction of EAE disease, with minimal inflammatory infiltrates in the central nervous system. These mice were resistant to EAE induction even when PLP(180−199) peptide specific effector T cells from BALB/c wild type were transferred to BALB/c T‐bet‐deficient mice. This resistance to EAE is may be caused by the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) from the spleen cells upon ex vivo stimulation with PLP(180−199) peptide and in vivo presence in the central nervous system. There was no difference in the recall responses in spleen cells from T‐bet‐deficient and wild type mice; however, less secretion of IFN‐γ was observed from primed splenocytes. The expression of IFN‐γ was less in the central nervous system of T‐bet‐deficient mice whereas IL‐10 was significantly higher in T‐bet‐deficient as compared to wild type mice. These data indicate that T‐bet genes play a critical role in maintaining the encephalitogenic nature of CD4+ T cells in autoimmune responses during EAE disease progression.