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1 January 2008 Repeated 0.5-Gy Gamma Irradiation Attenuates Autoimmune Disease in MRL-lpr/lpr Mice with Suppression of CD3 CD4CD8B220 T-Cell Proliferation and with Up-regulation of CD4 CD25 Foxp3 Regulatory T Cells
Fumitoshi Tago, Mitsutoshi Tsukimoto, Hiroko Nakatsukasa, Shuji Kojima
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Abstract

Tago, F., Tsukimoto, M., Nakatsukasa, H. and Kojima. S. Repeated 0.5 Gy Gamma Irradiation Attenuates Autoimmune Disease in MRL-lpr/lpr Mice with Suppression of CD3 CD4CD8B220 T-Cell Proliferation and with Up-regulation of CD4 CD25 Foxp3 Regulatory T Cells. Radiat. Res. 169, 59–66 (2008).

MRL-lpr/lpr mice are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MRL-lpr/lpr mice by repeated γ irradiation (0.5 Gy each time). In this study, we investigated the mechanisms of this attenuation by measuring the weight of the spleen and the population of highly activated CD3 CD4CD8B220 T cells, which are characteristically involved in autoimmune pathology in these mice. Splenomegaly and an increase in the percentage of CD3 CD4CD8B220 T cells, which occur with aging in nonirradiated mice, were suppressed in irradiated mice. The high proliferation rate of CD3 CD4CD8B220 T cells was suppressed in the irradiated animals. The production of autoantibodies and the level of IL6, which activates B cells, were also lowered by radiation exposure. These results indicate that progression of pathology is suppressed by repeated 0.5-Gy γ irradiation. To uncover the mechanism of the immune suppression, we measured the regulatory T cells, which suppress activated T cells and excessive autoimmune responses. We found that regulatory T cells were significantly increased in irradiated mice. We therefore conclude that repeated 0.5-Gy γ irradiation suppresses the proliferation rate of CD3 CD4CD8B220 T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.

Fumitoshi Tago, Mitsutoshi Tsukimoto, Hiroko Nakatsukasa, and Shuji Kojima "Repeated 0.5-Gy Gamma Irradiation Attenuates Autoimmune Disease in MRL-lpr/lpr Mice with Suppression of CD3 CD4CD8B220 T-Cell Proliferation and with Up-regulation of CD4 CD25 Foxp3 Regulatory T Cells," Radiation Research 169(1), 59-66, (1 January 2008). https://doi.org/10.1667/RR1013.1
Received: 6 March 2007; Accepted: 1 September 2007; Published: 1 January 2008
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