Increased susceptibility to immunologically mediated glomerulonephritis in IFN-gamma-deficient mice.
It is postulated that IFN-gamma confers susceptibility to immunologically mediated tissue injury. To test this hypothesis, we compared the intensity of accelerated anti-glomerular basement membrane glomerulonephritis between wild-type (IFN-gamma+/+) and IFN-gamma gene knockout (IFN-gamma-/-) mice. This disease model is initiated by binding of heterologous (sheep) anti-glomerular basement membrane Abs to the glomeruli of mice preimmunized with sheep IgG. The secondary cellular and humoral immune responses to the planted Ag then lead to albuminuria and glomerular pathology. We found that IFN-gamma-/- mice or IFN-gamma+/+ mice injected with IFN-gamma-neutralizing Ab develop worse albuminuria and glomerular pathology than IFN-gamma+/+ mice. The humoral response to sheep IgG (serum mouse anti-sheep IgG titers and intraglomerular mouse IgG deposits) was comparable in the IFN-gamma+/+ and IFN-gamma-/- groups. In contrast, IFN-gamma-/- mice mounted a stronger cellular immune response (cutaneous delayed-type hypersensitivity reaction) to sheep IgG than IFN-gamma+/+ mice. These findings provide evidence that endogenous IFN-gamma has a protective role in immunologically mediated glomerulonephritis initiated by foreign Ags.
Ring
G H
GH
Medical and Research Services, Veterans Affairs Medical Center, Renal Division, Department of Medicine, Emory University, Atlanta, GA 30033, USA.
Dai
Z
Z
Saleem
S
S
Baddoura
F K
FK
Lakkis
F G
FG
D000419:Albuminuria / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D002465:Cell Movement / Q000276:immunology; D004198:Disease Susceptibility; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D009566:Nitrates; D009573:Nitrites; C048844:anti-IgG; D007371:Interferon-gamma