Figure 3. Deleterious and beneficial roles of T cells in stroke.

In the acute phase of cerebral ischemia, unprimed T cells contribute to tissue damage in an antigen independent manner (innate immunity), possibly through IFNγ¹⁵¹ and ROS¹⁵² (left upper quadrant). γδT cells, activated by IL-23 released from microglia/macrophages, produce the cytotoxic cytokine IL-17 and contributes to acute ischemic brain injury⁴¹. However, T cells can also be protective. TGFβ produced by neurons, glia, or macroglia/macrophages promotes the development of T_reg cells secreting the protective cytokine IL-10 and inhibits Th1 and Th2 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 Th2 cells producing IL-10⁴⁸ and T_reg cells producing IL-10 and TGFβ^107,141 is highly protective in experimental stroke (right lower quadrant). As discussed in the text, there is no evidence that adaptive immunity contributes to acute ischemic brain injury. However, weeks and months after stroke, autoreactive CD4+ and CD8+ T cells targeting CNS antigens could develop (right upper quadrant). The resulting cell death could play a role in the delayed brain damage and atrophy that occurs after stroke⁸³.