Clinical and Experimental Nephrology

, Volume 15, Issue 1, pp 50–57

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

Authors

  • Kenro Miyasato
    • Department of Geriatric Medicine and NephrologyOsaka University Graduate School of Medicine
  • Yoshitsugu Takabatake
    • Department of Geriatric Medicine and NephrologyOsaka University Graduate School of Medicine
  • Junya Kaimori
    • Department of Advanced Technology for TransplantationOsaka University Graduate School of Medicine
  • Tomonori Kimura
    • Department of Geriatric Medicine and NephrologyOsaka University Graduate School of Medicine
  • Harumi Kitamura
    • Department of Geriatric Medicine and NephrologyOsaka University Graduate School of Medicine
  • Hiroshi Kawachi
    • Department of Cell Biology, Institute of NephrologyNiigata University Graduate School of Medical and Dental Sciences
  • Xiao-Kang Li
    • Laboratory of Transplantation ImmunologyNational Research Institute for Child Health and Development
  • Thomas Hünig
    • Institut für Virologie and ImmunobiologieUniverstät Würzburg
  • Shiro Takahara
    • Department of Advanced Technology for TransplantationOsaka University Graduate School of Medicine
  • Hiromi Rakugi
    • Department of Geriatric Medicine and NephrologyOsaka University Graduate School of Medicine
    • Department of Geriatric Medicine and NephrologyOsaka University Graduate School of Medicine
Original Article

DOI: 10.1007/s10157-010-0370-4

Cite this article as:
Miyasato, K., Takabatake, Y., Kaimori, J. et al. Clin Exp Nephrol (2011) 15: 50. doi:10.1007/s10157-010-0370-4

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.

Keywords

CD28Regulatory T cellFoxP3“Alternatively activated” macrophage

Copyright information

© Japanese Society of Nephrology 2010