| First Author | Odobasic D | Year | 2005 |
| Journal | Kidney Int | Volume | 68 |
| Issue | 2 | Pages | 584-94 |
| PubMed ID | 16014035 | Mgi Jnum | J:114308 |
| Mgi Id | MGI:3688765 | Doi | 10.1111/j.1523-1755.2005.00436.x |
| Citation | Odobasic D, et al. (2005) CD80 and CD86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms. Kidney Int 68(2):584-94 |
| abstractText | 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. |
