CD8 is down(regulated) for tolerance.

Activated CD8 T cells directly kill target cells. Therefore, the regulation of their function is central to avoiding immunopathology. Mechanisms that curb effector functions in CD4 and CD8 T cells are mostly shared, yet important differences occur. Here, we focus on the control of CD8 T cell activity and discuss the importance of a poorly understood aspect of tolerance that directly impairs engagement of target cells: the downregulation of CD8. We contextualize this process and propose that it represents a key element during CD8 T cell modulation.