Controlled autoimmunity in CNS maintenance and repair: naturally occurring CD4+CD25+ regulatory T-Cells at the crossroads of health and disease.

T-cells directed to self-antigens ("autoimmune" T-cells) have traditionally been perceived as tending to attack the body's own tissues, and likely to exert their destructive effects unless they undergo deletion in the thymus during ontogeny. Naturally occurring CD4+CD25+ regulatory T-cells were viewed as thymus-derived cells that constitutively suppress any autoimmune T-cells that escaped thymic deletion. Studies in recent years suggest, however, that some autoimmune T-cells are necessary, at least in the central nervous system for neural maintenance and repair, possibly in part by rendering the resident microglia capable of fighting off adverse conditions, as well as for neural maintenance and repair. In line with this notion, the regulatory T-cells are thought to allow autoimmunity to exist in healthy individuals without causing an autoimmune disease. This proposed immune scenario and its implications for therapy are discussed.