IL-12-dependent, INF-gamma-independent experimental glomerulonephritis.
There is evidence that crescentic glomerulonephritis initiated in rodents by heterologous antibodies against the glomerular basement membrane (anti-GBM glomerulonephritis) depends on a Th1-type immune reaction. Interleukin 12 (IL-12) is crucial for the development of Th1 helper cells, and interferon gamma (IFN-gamma) is a major proinflammatory product of these cells. In order to test the role of the two cytokines in anti-GBM glomerulonephritis we used mice lacking either the p40 chain of IL-12 (IL-12-/-) or the IFN-gamma receptor (IFN-gammaR-/-). Glomerulonephritis was induced by injecting a rabbit anti-GBM serum in mice preimmunized against rabbit IgG. Glomerulonephritis was assessed on the basis of proteinuria, immunofluorescence findings and histology. IL-12-/- mice were completely protected against glomerulonephritis. In contrast, IFN-gammaR-/- mice were more severely affected than wild-type mice. Similarly, cutaneous delayed-type hypersensitivity, a typical Th1 response, was abolished in the IL-12-/-, mice but increased in the IFN-gammaR-/- mice. The data obtained in IL-12-/- mice support the view that crescentic glomerulonephritis in this model represents a Th1 response. Since IFN-gamma is not required, other products of Th1 cells are likely to mediate glomerulonephritis.
Le Hir
M
M
Institute of Anatomy, University of Zürich, Switzerland. lehir@anatom.unizh.ch
Ryffel
B
B
Schatzmann
U
U
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology / Q000276:immunology*; D017353:Gene Deletion; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018664:Interleukin-12; D007371:Interferon-gamma