Repeated 0.5-Gy gamma irradiation attenuates autoimmune disease in MRL-lpr/lpr mice with suppression of CD3+CD4-CD8-B220+ T-cell proliferation and with up-regulation of CD4+CD25+Foxp3+ regulatory T cells.
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(+)CD4(-)CD8(-)B220(+) 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 gamma 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(+)CD4(-)CD8(-)B220(+) T cells, which are characteristically involved in autoimmune pathology in these mice. Splenomegaly and an increase in the percentage of CD3(+)CD4(-)CD8(-)B220(+) T cells, which occur with aging in nonirradiated mice, were suppressed in irradiated mice. The high proliferation rate of CD3(+)CD4(-)CD8(-)B220(+) 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 gamma 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 gamma irradiation suppresses the proliferation rate of CD3(+)CD4(-)CD8(-)B220(+) T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.
Tago
Fumitoshi
F
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki Noda-shi Chiba, 278-8510, Japan.
Tsukimoto
Mitsutoshi
M
Nakatsukasa
Hiroko
H
Kojima
Shuji
S
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005720:Gamma Rays; D015850:Interleukin-6 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009929:Organ Size / Q000528:radiation effects; D013163:Splenomegaly / Q000473:pathology / Q000532:radiotherapy; D015854:Up-Regulation
D001323:Autoantibodies; D017252:CD3 Complex; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D017493:Leukocyte Common Antigens