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Regulatory T cells participate in several immune responses including autoimmune reactions inducing selftolerance, tumor immunity, transplantation tolerance and microbial infection. Nevertheless, regulatory T cells actions seem to be different when they are in the central nervous system (CNS), since they interact with resident cells of the CNS, according to the particular conditions elicited in this compartment. This review focuses on the role of regulatory T cells in health, autoimmune and other CNS diseases, pointing out their interactions with resident CNS cells.