41: γβ T cells, a novel T cell subset with a pathogenic role in IL-17-mediated CNS autoimmunity

V γ 4 + T cells have been identified as the main IL-17-producing γ δ T cell in the CNS of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The findings of this study demonstrate that V γ 4 + T cells are present in T cell receptor (TCR) δ - / - mice, and furthermore these V γ 4 + T cells co-express TCR β . The data reveals that V γ 4 β T cells respond to IL-1 β and IL-23 stimulation in the absence of TCR engagement to produce IL-17A and IL-17F and express the master transcription factor, ROR γ t and the integrin, MCAM. Furthermore, V γ 4 β + T cells, together with conventional V γ 4 δ + T cells were found in the brains of mice with EAE. V γ 4 β + T cells were also found in the brains TCR δ - / - mice with EAE. Although, the course of EAE is somewhat reduced in TCR δ - / - compared with wild type (WT) mice, depletion of V γ 4 + T cells from TCR δ - / - as well as WT mice significantly attenuated clinical disease and weight loss in mice with EAE. Anti-V γ 4 treated mice with EAE had a significantly reduced frequency of infiltrating IL-17 + , IFN- γ + and IFN- γ + IL-17 + CD4 + T cells into CNS. Furthermore, in the adoptive transfer model of EAE, depletion of V γ 4 + cells from lymph node and spleen cells from TCR δ - / - mice significantly impair their ability to induce EAE, with a reduction in inflammatory T cells infiltrating the CNS. Our study has identified a novel γ β T cell subset, V γ 4 β T cells, which together with conventional V γ 4 δ T cells, play a critical role in the pathogenesis of EAE through innate IL-17 production, necessary to enhance Th17 and Th1 activation and migration into the CNS to mediate inflammation and autoimmunity.