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Citations to this article

CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis
John Reynolds, … , Mohamed H. Sayegh, Charles D. Pusey
John Reynolds, … , Mohamed H. Sayegh, Charles D. Pusey
Published March 1, 2000
Citation Information: J Clin Invest. 2000;105(5):643-651. https://doi.org/10.1172/JCI6710.
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Article

CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis

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Abstract

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The role of T cells in the pathogenesis of EAG remains unclear. T-cell costimulation is provided by ligation of CD28 with either B7.1 (CD80) or B7.2 (CD86) on antigen-presenting cells, and can be inhibited by a soluble form of CTLA4 (CTLA4-Ig) that binds to both B7.1 and B7.2. We examined the effect of CD28-B7 blockade on the development of EAG using native CTLA4-Ig or mutant CTLA4-Ig (Y100F-Ig), which selectively blocks B7.1. Native CTLA4-Ig treatment ameliorated EAG by several measures, including the levels of circulating anti-GBM antibodies, albuminuria, the deposition of IgG and fibrin in the glomeruli, the severity of glomerular abnormalities, and the numbers of infiltrating T cells and macrophages. Y100F-Ig resulted in a similar reduction in the severity of nephritis, but produced no overall reduction in circulating anti-GBM antibodies, although there was a reduction in IgG2a antibodies. We concluded that CD28-B7 blockade reduced autoantibody production and cellular infiltration of glomeruli, and prevented target organ injury. Our results suggest a key role for B7.1 in costimulation of Th1-like autoimmune responses in the rat, and show that glomerular injury in EAG is largely dependent on cell-mediated mechanisms.

Authors

John Reynolds, Frederick W.K. Tam, Anil Chandraker, Jennifer Smith, Ayman M. Karkar, Jane Cross, Robert Peach, Mohamed H. Sayegh, Charles D. Pusey

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Journal of immunology (Baltimore, Md. : 1950) 2001
Oral Administration of Glomerular Basement Membrane Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat
J Reynolds, CD Pusey
Journal of the American Society of Nephrology : JASN 2001
In Goodpasture's Disease, CD4 + T Cells Escape Thymic Deletion and Are Reactive with the Autoantigen α3(IV)NC1
AD Salama, AN Chaudhry, JJ Ryan, E Eren, JB Levy, CD Pusey, L Lightstone, RI Lechler
Journal of the American Society of Nephrology : JASN 2001
Interleukin-11 Attenuates Nephrotoxic Nephritis in Wistar Kyoto Rats
PC Lai, HT Cook, J Smith, JC Keith, CD Pusey, FW Tam
Journal of the American Society of Nephrology : JASN 2001
CTLA4-Ig: a novel immunosuppressive agent
N Najafian, MH Sayegh
Expert Opinion on Investigational Drugs 2000
Uveitis
CE Egwuagu, JA Smith
Expert Opinion on Therapeutic Targets 2000
Authors' reply:
Y Hisada, T Sugaya
American Journal of Kidney Diseases 2000
Bacterial Pathogens Induce Abscess Formation by CD4 + T-Cell Activation via the CD28–B7-2 Costimulatory Pathway
EI Tuomanen, AO Tzianabos, A Chandraker, W Kalka-Moll, F Stingele, VM Dong, RW Finberg, R Peach, MH Sayegh
Infection and immunity 2000
Gene therapy for autoimmune disorders
C H Evans, S C Ghivizzani, T J Oligino, P D Robbins
Journal of Clinical Immunology 2000
Immunotherapy for autoimmune and inflammatory renal diseases
DR Jayne
Current Opinion in Nephrology and Hypertension 1998

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