title: CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  We established a new therapeutic approach to suppressing progressive glomerulonephritis. The therapeutic value of this approach warrants further attention and preclinical studies.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenro
authors.initials: K
authors.lastname: Miyasato
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Takabatake
authors.forename: Junya
authors.initials: J
authors.lastname: Kaimori
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kimura
authors.forename: Harumi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000276:immunology*; D003404:Creatinine / Q000097:blood; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D003404:Creatinine