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

Fumitoshi Tago, Mitsutoshi Tsukimoto, Hiroko Nakatsukasa, Shuji Kojima

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28 Citations (Scopus)

Abstract

MRL-lpr/lpr mice are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MKL-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+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 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+CD4-CD8 -B220+ T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalRadiation Research
Volume169
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1
Externally publishedYes

Fingerprint

autoimmune diseases
Regulatory T-Lymphocytes
Autoimmune Diseases
gamma radiation
mice
cell proliferation
Up-Regulation
T-lymphocytes
Cell Proliferation
retarding
T-Lymphocytes
irradiation
Autoantibodies
Interleukin-6
pathology
Pathology
Splenomegaly
attenuation
Autoimmunity
lupus erythematosus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

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title = "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",
abstract = "MRL-lpr/lpr mice are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MKL-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+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 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+CD4-CD8 -B220+ T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.",
author = "Fumitoshi Tago and Mitsutoshi Tsukimoto and Hiroko Nakatsukasa and Shuji Kojima",
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T1 - 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

AU - Tago, Fumitoshi

AU - Tsukimoto, Mitsutoshi

AU - Nakatsukasa, Hiroko

AU - Kojima, Shuji

PY - 2008/1/1

Y1 - 2008/1/1

N2 - MRL-lpr/lpr mice are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MKL-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+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 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+CD4-CD8 -B220+ T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.

AB - MRL-lpr/lpr mice are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MKL-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+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 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+CD4-CD8 -B220+ T cells and the production of IL6 and autoantibodies and up-regulates regulatory T cells.

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