Double-negative T cells remarkably promote neuroinflammation after ischemic stroke

Significance In the present study, we found a significantly up-regulated CD3 + CD4 − CD8 − T cell (double-negative T cell; DNT) population in the peripheral blood of patients with acute stroke compared with age-matched healthy subjects. Interestingly, infiltrating DNTs were mainly located close to microglia in the ischemic brain tissues of both stroke patients and middle cerebral artery occlusion mice. DNTs amplified the proinflammatory microglia and subsequently enhanced the neuroinflammation and exacerbated the brain injury after ischemic stroke. Mechanistically, DNT-intrinsic FasL and PTPN2 collaboratively regulate the level of CD86 + microglia via production of TNF-α. Taken together, these data reveal that infiltrating DNTs are the critical driving force in promoting microglia-mediated neuroinflammation and ischemic brain injury.