Vγ1 and Vγ4 γδ T cell subsets play opposing roles in traumatic brain injury

Abstract Traumatic brain injury (TBI) results in both morbidity and mortality in which both innate and adaptive immune responses play an important role in the pathogenesis of TBI. Nonetheless, the role of gamma-delta (γδ) T cells in acute and chronic TBI is unknown. Here, we show that γδ T cells affect the pathophysiology of TBI as early as one day and up to one year after injury. TCRδ−/− mice exhibited reduced inflammation in acute TBI and improved neurocognitive functions in chronic TBI. We found that Vγ1 and Vγ4 γδ T cell subsets played opposing roles in TBI. Vγ4 γδ T cells infiltrate the brain and secrete IFN-γ and IL-17 that activate microglia and induce neuroinflammation, whereas Vγ1 γδ T cells infiltrate the brain and secrete TGF-β that maintains microglial homeostasis and dampens TBI. These findings provide new insights on the role of different γδ T cell subsets after brain injury and provide novel avenues for the development of targeted γδ T-cell-based therapy for the treatment of TBI.