CD80 and CD86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-08

AUTHORS

Dragana Odobasic, A Richard Kitching, Peter G Tipping, Stephen R Holdsworth

ABSTRACT

BACKGROUND: CD80 and CD86 costimulatory molecules have been shown to affect the induction of Th1-mediated crescentic antiglomerular basement membrane (GBM) antibody-initiated glomerulonephritis (GN). The aim of the current studies was to define the mechanisms by which CD80 and CD86 regulate the development of this disease. METHODS: Anti-GBM GN was induced in CD80-/-, CD86-/-, and CD80/86-/- mice, as well as in C57BL/6 controls. Renal injury and immune responses were assessed after 21 days. To examine whether costimulation by OX40-ligand compensates for the absence of CD80 and CD86 in inducing GN, OX40-ligand was blocked in wild-type and CD80/86-/- mice. RESULTS: Crescentic GN and glomerular accumulation of CD4+ T cells and macrophages were attenuated in CD80-/- mice, correlating with significantly enhanced apoptosis and decreased proliferation of spleen CD4+ T cells. GN was exacerbated in CD86-/- mice, which was associated with attenuated IL-4 and enhanced IFN-gamma levels. In contrast, CD80/86-/- mice developed crescentic GN similar to that in controls. Inhibition of OX40-ligand exacerbated GN in wild-type mice by enhancing IFN-gamma production, and attenuated disease in CD80/86-/- mice by reducing glomerular CD4+ T-cell and macrophage accumulation. CONCLUSION: CD80 is pathogenic in crescentic GN by enhancing survival and proliferation of CD4+ T cells, whereas CD86 is protective by enhancing Th2 and attenuating Th1 responses. Furthermore, in the presence of CD80 and CD86, OX40-ligand attenuates, whereas in their absence it enhances GN, suggesting that, in the absence of CD80 and CD86, the OX40/OX40-ligand pathway is an alternative costimulatory pathway in inducing crescentic GN. More... »

PAGES

584-594

Identifiers

URI

http://scigraph.springernature.com/pub.10.1111/j.1523-1755.2005.00436.x

DOI

http://dx.doi.org/10.1111/j.1523-1755.2005.00436.x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006998031

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16014035


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