MHC antigens in interferon gamma (IFN gamma) receptor deficient mice: IFN gamma-dependent up-regulation of MHC class II in renal tubules.
MHC class II gene products in parenchymal cells, such as tubular epithelial cells in kidney, may play a role in the regulation of autoimmune reactions. Expression of MHC class II in renal tubular cells is normally very low, but it increases considerably under various pathologic conditions. The predominant role of IFN gamma in up-regulation of MHC class II expression has been demonstrated repeatedly. We tested the existence of alternative pathways of MHC class II regulation using IFN gamma receptor-deficient (IFN gamma R-/-) mice. Mutant and wild type mice received 50 micrograms bacterial endotoxin (LPS) i.p. Four days later the kidneys were removed for immunofluorescence examination. In agreement with published results LPS provoked an increase of immunoreactivity for MHC class I and MHC class II in proximal tubules of wild type mice. While MHC class I up-regulation was strictly IFN gamma receptor-dependent, up-regulation of MHC II was still evident in mutant mice, although less than in wild type mice. Since injection of IFN gamma induced proximal tubular MHC class II expression in wild type mice but not in IFN gamma R-/- mice, an alternative signaling pathway for IFN gamma does not seem to exist. Thus, up-regulation of MHC class II expression in renal tubules does not necessarily require IFN gamma. The markedly patchy pattern of immunofluorescence in IFN gamma R-/- mice suggests that induction of MHC class II after LPS injection may represent renal injury due to shock.
Haas
C
C
Institute of Toxicology, University and Federal School of Technology, Zürich, Switzerland.
Ryffel
B
B
Aguet
M
M
Le Hir
M
M
D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D005260:Female; D005805:Genes, MHC Class I / Q000187:drug effects / Q000502:physiology; D005802:Genes, MHC Class II / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D017471:Receptors, Interferon / Q000172:deficiency*; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D007371:Interferon-gamma; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor