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Clinical and Experimental Nephrology

, Volume 15, Issue 1, pp 50–57 | Cite as

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

  • Kenro Miyasato
  • Yoshitsugu Takabatake
  • Junya Kaimori
  • Tomonori Kimura
  • Harumi Kitamura
  • Hiroshi Kawachi
  • Xiao-Kang Li
  • Thomas Hünig
  • Shiro Takahara
  • Hiromi Rakugi
  • Yoshitaka IsakaEmail author
Original Article

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

CD28 Regulatory T cell FoxP3 “Alternatively activated” macrophage 

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Copyright information

© Japanese Society of Nephrology 2010

Authors and Affiliations

  • Kenro Miyasato
    • 1
  • Yoshitsugu Takabatake
    • 1
  • Junya Kaimori
    • 2
  • Tomonori Kimura
    • 1
  • Harumi Kitamura
    • 1
  • Hiroshi Kawachi
    • 3
  • Xiao-Kang Li
    • 4
  • Thomas Hünig
    • 5
  • Shiro Takahara
    • 2
  • Hiromi Rakugi
    • 1
  • Yoshitaka Isaka
    • 1
    Email author
  1. 1.Department of Geriatric Medicine and NephrologyOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Department of Advanced Technology for TransplantationOsaka University Graduate School of MedicineSuitaJapan
  3. 3.Department of Cell Biology, Institute of NephrologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  4. 4.Laboratory of Transplantation ImmunologyNational Research Institute for Child Health and DevelopmentTokyoJapan
  5. 5.Institut für Virologie and ImmunobiologieUniverstät WürzburgWürzburgGermany

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