Regulation of MHC expression in vivo. Bacterial lipopolysaccharide induces class I and II MHC products in mouse tissues by a T cell-independent, cyclosporine-sensitive mechanism.
The effect of injections of bacterial LPS on the expression of class I and II products of the MHC in mouse tissues was investigated. MHC products were assessed in tissue homogenates by radiolabeled antibody binding and in tissue sections by indirect immunoperoxidase (IIP) staining. In mice given two i.p. injections of LPS from Escherichia coli or Salmonella minnesota, there were increases in class I and II MHC products in kidney, liver, heart, lung, and pancreas. Focusing on the changes in kidney, we demonstrated that the increase in MHC expression occurred in tubules and, in the case of class I, in glomeruli. LPS treatment also increased the deposition of Ig in glomeruli. Expressed on a standard curve, the total kidney class I and II expression was elevated approximately 10-fold. Time course studies indicated that increased class I expression could be induced by a single LPS injection, whereas class II induction required a second injection. The induction was influenced by the LPS sensitivity of the mice, being much greater in LPS-sensitive C3H/HeSn mice than in LPS-resistant C3H/HeJ mice. LPS induced class I and II Ag in nude mice and in mice with severe combined immunodeficiency, indicating that T cells were not required. Nevertheless, the effect of LPS was inhibitable by cyclosporine and by a mAb against IFN-gamma indicating that IFN-gamma was required for the MHC induction. We conclude that LPS induces an increase in expression and a redistribution of MHC products in kidney and in other tissues by a T cell-independent, cyclosporine-sensitive pathway. These findings are probably related to the known ability of LPS to mediate release of IFN-gamma and other cytokines.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000918:Antibody Specificity; D000955:Antigens, T-Independent / Q000276:immunology*; D001666:Binding Sites, Antibody; D003524:Cyclosporins / Q000008:administration & dosage*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology; D007668:Kidney / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008285:Major Histocompatibility Complex / Q000187:drug effects*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D003524:Cyclosporins; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D007371:Interferon-gamma