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. T...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-08, Vol.163 (4), p.2243-2248
Main Authors: Ring, G H, Dai, Z, Saleem, S, Baddoura, F K, Lakkis, F G
Format: Article
Language:English
Subjects:
Albuminuria - genetics
Albuminuria - immunology
Albuminuria - pathology
Animals
Anti-Glomerular Basement Membrane Disease - genetics
Anti-Glomerular Basement Membrane Disease - immunology
Anti-Glomerular Basement Membrane Disease - pathology
Antibodies, Anti-Idiotypic - biosynthesis
Basement Membrane - immunology
Basement Membrane - metabolism
Binding Sites, Antibody
Cell Movement - immunology
Disease Susceptibility
Hypersensitivity, Delayed - immunology
Immunoglobulin G - immunology
Interferon-gamma - deficiency
Interferon-gamma - genetics
Kidney Glomerulus - immunology
Kidney Glomerulus - metabolism
Kidney Glomerulus - pathology
Macrophages - pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes - pathology
Neutrophils - pathology
Nitrates - urine
Nitrites - urine
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.163.4.2243