Crescentic glomerulonephritis in interferon-gamma receptor deficient mice

Activation of macrophages by T cells is considered an initiating event in glomerular crescent formation. Since interferon-gamma (INF gamma) is a key mediator in T-cell-mediated activation of macrophages, we decided to test its role in a model of crescentic glomerulonephritis. An anti-glomerular basement membrane (GBM) serum was injected intravenously in presensitized wild-type or IFN gamma receptor deficient (IFN gamma(R)-/-) mice. Glomerulonephritis with glomerular crescents and tubulointerstitial inflammation developed in both strains, even though most evaluated morphological parameters and proteinuria indicated a less severe pathology in the mutant mice compared to the wild type. Thus, IFN gamma is not essential either for glomerular crescent formation or for tubulointerstitial involvement in anti-GBM glomerulonephritis in mice. In conclusion, the role of macrophages in this model might have been overestimated, or other cytokines may compensate for deficient IFN gamma signaling in the activation of macrophages.