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.
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-Thy1nephritis 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.
Authors: Ganesh Suntharalingam; Meghan R Perry; Stephen Ward; Stephen J Brett; Andrew Castello-Cortes; Michael D Brunner; Nicki Panoskaltsis Journal: N Engl J Med Date: 2006-08-14 Impact factor: 91.245
Authors: Yuan Min Wang; Geoff Yu Zhang; Yiping Wang; Min Hu; Huiling Wu; Debbie Watson; Shohei Hori; Ian E Alexander; David C H Harris; Stephen I Alexander Journal: J Am Soc Nephrol Date: 2006-02-08 Impact factor: 10.121
Authors: Machteld M Tiemessen; Ann L Jagger; Hayley G Evans; Martijn J C van Herwijnen; Susan John; Leonie S Taams Journal: Proc Natl Acad Sci U S A Date: 2007-11-27 Impact factor: 11.205
Authors: H Azuma; Y Isaka; X Li; T Hünig; T Sakamoto; H Nohmi; Y Takabatake; M Mizui; Y Kitazawa; N Ichimaru; N Ibuki; T Ubai; T Inamoto; Y Katsuoka; S Takahara Journal: Am J Transplant Date: 2008-07-22 Impact factor: 8.086