CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis

The HLA-DRB1*15

“…The identification of a key epitope paves the way for studies that examine the nature of the intra-and intermolecular epitope spreading seen in this disease. 2,16,40,41 Although autoimmune anti-GBM GN has been modeled in a number of animal species, 5,6,42,43 the most commonly used model injects human a3(IV)NC1 or rat a3(IV)NC1 peptides into WKY rats 7,15,16 that carry genetic susceptibilities rendering them vulnerable to various aspects of experimental GN. 23,24 Although mice develop autoimmunity to a3(IV)NC1 and may develop disease after approximately 10 weeks, 9,39,44 severe disease in mice has been more difficult to establish.…”

T cell infiltration is associated with kidney injury in patients with anti-glomerular basement membrane disease

“…The disease cannot be induced in CD4 + and CD8 + T cell knockout mice (Tipping et al, 1998) and is inhibited by CD28-B7 and CD154-CD40 co-stimulatory blockades (Reynolds et al, 2000(Reynolds et al, , 2004 as well as anti-CD8 monoclonal antibodies (Reynolds et al, 2002). Additionally, a Th17 cell subset, which is maintained by IL-23, plays a dominant role in the development of anti-GBM disease.…”

Antibodies against Linear Epitopes on the Goodpasture Autoantigen and Kidney Injury

“…In vitro studies have shown that peripheral CD4 + T cells in anti-GBM patients proliferated with the same autoantigen of a3(IV)NC1 recognized by anti-GBM antibodies (14). In animal models either lacking T cells or with an interrupted B7/CD28 costimulation pathway, experimental crescentic GN is alleviated (15)(16)(17). Direct evidence comes from the passive transfer studies showing that in the absence of anti-GBM antibodies, the antigen-specific CD4 + T cells per se could initiate kidney injury (18).…”