MHC antigens in interferon γ (IFNγ) receptor deficient mice: IFNγ-independent up-regulation of MHC class II in renal tubules

Abstract

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 IFNγ 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 IFNγ receptor-deficient (IFNγR-/-) mice. Mutant and wild type mice received 50 μg 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 IFNγ receptor-dependent, up-regulation of MHC II was still evident in mutant mice, although less than in wild type mice. Since injection of IFNγ induced proximal tubular MHC class II expression in wild type mice but not in IFNγR-/- mice, an alternative signaling pathway for IFNγ does not seem to exist. Thus, up-regulation of MHC class II expression in renal tubules does not necessarily require IFNγ. The markedly patchy pattern of immunofluorescence in IFNγR-/- mice suggests that induction of MHC class II after LPS injection may represent renal injury due to shock.