Fig. 8. Role of CD8⁺ T cells in the pathophysiology of SuS.

Working model of role of CD8⁺ T cells in the pathophysiology of SuS. A yet unknown antigenic stimulus drives activation, clonal expansion, and differentiation of CD8⁺ T cells into GrB- and perforin-expressing CD8⁺ T_EMRA cells. CD8⁺ T cells accumulate in microvessels of the brain, retina, and inner ear, where they adhere to the endothelium, recognize HLA:peptide complex(es), polarize their cytolytic vesicles toward the endothelial plasma cell membrane, and induce apoptosis of ECs, most likely in a perforin/GrB-dependent manner. Death of ECs and focal disruption of the blood–brain barrier result in microhemorrhages, whereas occlusion of small blood vessels leads to small ischemic lesions with loss of astrocytes, oligodendrocytes, neurons, and axons. Finally, ischemic lesions become gliotic by infiltration of surrounding astrocytes. Illustration^©2019-Heike Blum, Department of Neurology with Institute of Translational Neurology, University Hospital Münster.