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01-02-2011 | Original Article

CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats

Authors: Kenro Miyasato, Yoshitsugu Takabatake, Junya Kaimori, Tomonori Kimura, Harumi Kitamura, Hiroshi Kawachi, Xiao-Kang Li, Thomas Hünig, Shiro Takahara, Hiromi Rakugi, Yoshitaka Isaka

Published in: Clinical and Experimental Nephrology | Issue 1/2011

Abstract

Background

Naturally occurring regulatory T cells (Treg) are essential for the prevention of autoimmunity and overshooting immune responses to pathogens; however, the involvement of Treg in mesangioproliferative glomerulonephritis, a major cause of chronic kidney disease, remains unclear. Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of Treg in rats.

Method

To confirm our hypothesis that CD28SA reduces the severity of experimental glomerulonephritis, anti-Thy1 nephritis model rats were treated with CD28SA or saline.

Results

CD28SA significantly suppressed the increase in proteinuria and serum creatinine levels. CD28SA-treated nephritic rats exhibited an increase in the infiltration of Treg in the glomeruli accompanied by infiltration of CD163-positive macrophages (“alternatively activated” macrophages). In addition, CD28SA significantly induced interleukin-10 mRNA expression in glomeruli, thereby ameliorating mesangial cell proliferation and extracellular matrix expansion.

Conclusion

We established a new therapeutic approach to suppressing progressive glomerulonephritis. The therapeutic value of this approach warrants further attention and preclinical studies.

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Title: CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats
Authors: Kenro Miyasato
Yoshitsugu Takabatake
Junya Kaimori
Tomonori Kimura
Harumi Kitamura
Hiroshi Kawachi
Xiao-Kang Li
Thomas Hünig
Shiro Takahara
Hiromi Rakugi
Yoshitaka Isaka
Publication date: 01-02-2011
Publisher: Springer Japan
Published in: Clinical and Experimental Nephrology / Issue 1/2011
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-010-0370-4

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CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats

Abstract

Background

Method

Results

Conclusion

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Abstract

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Conclusion

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