Repeated gamma irradiation attenuates collagen-induced arthritis via up-regulation of regulatory T cells but not by damaging lymphocytes directly.

We recently reported that repeated 0.5-Gy gamma irradiation attenuates the pathology of collagen-induced arthritis. In this study, to investigate the mechanism further, we focused on changes in Treg/Th17 cells and changes in the production of antibody against an external antigen in response to gamma irradiation as well as on the radiosensitivity of Treg cells. DBA/1J mice were immunized with type II collagen to induce arthritis and exposed to low-dose gamma rays (0.5 Gy/week for 5 weeks). Production of IL6 and IL17 as well as autoantibody was suppressed by irradiation in the early phase of collagen-induced arthritis. The percentage of Treg cells was significantly increased by irradiation at 4, 6 and 8 weeks after the immunization. We also investigated the effect of repeated gamma radiation on the production of antibodies against an external antigen in ovalbumin-immunized BALB/c mice. We found that repeated 0.5-Gy gamma irradiation enhanced antibody production, accompanied by an increase of the antibody-producing plasma cell population and increased Th2-type cytokine secretion. We also found that the radiosensitivity of Treg cells did not differ from that of other T cells. These results suggest that a major mechanism of attenuation of the pathology of collagen-induced arthritis by repeated 0.5-Gy gamma irradiation is up-regulation of Treg cells concomitantly with suppression of IL6 and IL17 production.