Long-Term Accumulation of T Cytotoxic 1, T Cytotoxic 17, and T Cytotoxic 17/1 Cells in the Brain Contributes to Microglia-Mediated Chronic Neuroinflammation After Ischemic Stroke

Abstract

Post-stroke neuroinflammation affects the damage and recovery of neurological functions. T cells including CD8⁺ T cells were present in the ipsilateral hemisphere in the subacute and late phases of ischemic stroke. However, the potential roles of CD8⁺ T cell subsets in the progression of neuroinflammation have not been characterized. In the current mouse transient middle cerebral artery occlusion model, we investigated the existence of CD8⁺ T cell subsets in the ipsilateral hemisphere in the subacute and late phases of stroke. We found that ipsilateral CD8⁺ T cells were present on post-stroke day 3 and increased on post-stroke day 30. The day-3 ipsilateral CD8⁺ T cells predominantly produced interferon-γ (IFN-γ), while the day-30 ipsilateral CD8⁺ T cells co-expressed IFN-γ and interleukin-17A (IL-17A). In addition, evaluation of cytokines and transcription factors of the day-30 ipsilateral CD8⁺ T cells revealed the presence of T cytotoxic 1 (Tc1), T cytotoxic 17 (Tc17), and T cytotoxic 17/1 (Tc17/1) cells. Furthermore, based on the expression of a series of chemokine/cytokine receptors, viable ipsilateral Tc1, Tc17, and Tc17.1 cells were identified and enriched from the day-30 ipsilateral CD8⁺ T cells, respectively. Co-culture of microglia with ipsilateral Tc1, Tc17, or Tc17.1 cells indicated that the three CD8⁺ T cell subsets up-regulated the expression of pro-inflammatory mediators by microglia, with Tc17.1 cells being the most potent cell in doing so. Collectively, this study sheds light on the contributions of Tc1, Tc17, and Tc17.1 cells to long-term neuroinflammation after ischemic stroke.

Keywords: Brain; CD8+ T cells; Immunity; Ischemic stroke; Neuroinflammation.