25 years of UV-induced immunosuppression mediated by T cells-from disregarded T suppressor cells to highly respected regulatory T cells.

For more than 25 years it is known that UV radiation, in particular the UVB range suppresses the immune system. In contrast to conventional immunosuppression by immunosuppressive drugs, UV radiation does not compromise the immune system in a general but rather in an antigen-specific fashion via induction of immunotolerance. This effect is mostly mediated via regulatory T cells (Treg) induced by UV. Several subtypes of UV-induced Treg may exist, the best characterized are those which inhibit contact hypersensitivity. Induction of these Tregs by UV radiation is an active process which requires antigen presentation by UV-damaged but still alive Langerhans cells (LC) in the lymph nodes. UV-induced Treg have recently been characterized as expressing CD4 and CD25 and as releasing upon activation the immunosuppressive cytokine interleukin (IL)-10. Once activated in an antigen-specific manner, they suppress immune responses in a general fashion via the release of IL-10, a phenomenon called bystander suppression. The further phenotypic and functional characterization of these cells will not only contribute to a better understanding of the impact of UV radiation on the immune system but will also determine whether they can be applied in the future therapeutically with the final aim of achieving specific immunosuppression.