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[en] Complete text of publication follows. MRL-lpr/lpr mice present a single gene mutation on the Fas (CD95) gene that leads to reduced signaling for apoptosis. With aging, these mice spontaneously develop autoimmune disease and are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MRL-lpr/lpr mice by repeated γ-ray irradiation (0.5 Gy each time). In this study, we investigated the mechanisms of this attenuation focusing the highly activated CD3+CD4-CD8-B220+ T cells, which are characteristically involved in autoimmune pathology in these mice. We measured the weight of the spleen and the population of CD3+CD4-CD8-B220+ T cells. Splenomegaly and increase in percentage of CD3+CD4-CD8-B220+ T cells, which occur with aging in non-irradiated mice, were suppressed in irradiated mice. To investigate the function of CD3+CD4-CD8-B220+ T cells, we isolated these cells from splenocytes by magnetic cell sorting. Isolated CD3+CD4-CD8-B220+ T cells were more resistant to irradiation-induced cell death than isolated CD4+ T cells. Although high proliferation rate and IL-6 production were observed in isolated CD3+CD4-CD8-B220+ T cells, the proliferation rate and IL-6 production were lower in the cells isolated from the irradiated mice. Moreover, the production of autoantibodies (anti-collagen antibody and anti-single strand DNA antibody) was also lowered by irradiation. These results indicate that activation of CD3+CD4-CD8-B220+ T cells and progression of pathology would be suppressed by repeated 0.5 Gy γ-ray irradiation. To uncover the mechanism of the immune suppression, we analyzed population of regulatory T cells (CD4+CD25+Foxp3+), which suppress activated T cells and excessive autoimmune responses. Intriguingly, significant increase of the percentage of regulatory T cells was observed in irradiated mice. In conclusion, we found that repeated 0.5 Gy γ-ray irradiation suppresses proliferation rate of CD3+CD4-CD8-B220+ T cells and productions of IL-6 and autoantibodies, and up-regulates regulatory T cells. These results indicate that up-regulation of regulatory T cells would involve in these therapeutic effects induced by irradiation. The up-regulation of regulatory T cells induced by irradiation could be a novel and important observation in low-dose irradiation-mediated therapeutic effects.