Deleterious and beneficial roles of T cells in stroke. : The immunology of stroke: from mechanisms t

In the acute phase of cerebral ischemia, unprimed T cells contribute to tissue damage in an antigen-independent manner (innate immunity), possibly through IFN-γ¹¹⁰ and ROS¹¹¹ (top left). γδT cells, activated by IL-23 released from microglia and macrophages, produce the cytotoxic cytokine IL-17 and contribute to acute ischemic brain injury⁴¹. However, T cells can also be protective. TGF-β produced by neurons, glia, or microglia and macrophages promotes the development of T_reg cells secreting the protective cytokine IL-10 and inhibits T_H1 and T_H2 responses. T_reg cells are protective in models of cerebral ischemia⁴². Induction of mucosal tolerance with CNS antigens produces an adaptive response, which leads to the establishment of autoreactive T_H2 cells producing IL-10 (ref. 48) and T_reg cells producing IL-10 and TGF-β¹⁰⁷ is highly protective in experimental stroke (bottom right). Although there is no evidence that adaptive immunity contributes to acute ischemic brain injury, weeks and months after stroke, autoreactive CD4⁺ and CD8⁺ T cells targeting CNS antigens could develop (top right). The resulting cell death could play a part in the delayed brain damage and atrophy that occur after stroke⁸³.