Post-immune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses

Abstract

It is well documented that UV radiation present in sunlight suppresses immune responses, especially T(h)1-driven cellular immune responses, resulting in the exacerbation of skin cancer and infectious diseases. However, the effects of UV irradiation on humoral immune responses remain less clearly defined. In addition, the majority of studies documenting immunosuppressive effects of UV irradiation has been demonstrated in animals exposed to UV radiation before immunization. In the present study, therefore, we examined the effects of UV irradiation on humoral immune responses in mice that had been immunized before UV irradiation. Both T(h)1- and T(h)2-associated Ig responses were significantly suppressed by UV irradiation given 7 days after immunization in an antigen-specific manner. Adoptive transfer experiments revealed that CD4(+) T cells from UV-irradiated mice are responsible for the UV-induced suppression of antibody responses. These CD4(+) regulatory T cells suppressed proliferation of conventional CD4(+) T cells in vivo and in vitro and contained IL-10-producing cells that did not express Foxp3. Mice depleted of CD25(+) cells also exhibited reduced antibody responses by UV irradiation. Finally, we showed that CD4(+) T cells from UV-irradiated mice treated with anti-IL-10 mAb failed to suppress antibody responses upon transfer. These results indicate that UV irradiation after immunization suppresses T(h)1- and T(h)2-mediated humoral immunity via the generation of Tr1-like regulatory T cells, in the process of which IL-10 appears to be important. Possible detrimental effects of UV irradiation after vaccination are also discussed.