Regulation of MHC expression in vivo. II. IFN-alpha/beta inducers and recombinant IFN-alpha modulate MHC antigen expression in mouse tissues.
We examined the effect of type I IFN inducers and rIFN-alpha on MHC expression in mouse tissues in vivo. MHC expression was assessed in a radiolabeled mAb binding assay and by indirect immunoperoxidase staining of tissue sections. polyI:C, an inducer of IFN-alpha/beta, induced large increases in class I MHC in many tissues, with little effect on class II expression. In the kidney, which was studied in detail, polyI:C increased class I expression from day 1 to day 6, localized in glomeruli, tubules, and arterial endothelium. Renal class II MHC was less affected but tended to be decreased at days 3 to 6, corresponding to diminished staining of class II-positive interstitial cells. polyI:C increased renal class I MHC in nude mice and mice with severe combined immunodeficiency, and in mice treated with cyclosporine or mAb against IFN-gamma. The effects of influenza virus resembled those of polyI:C. However, a potent T cell stimulus, allogeneic ascites tumor cells, induced markedly different MHC changes, with massive and sustained increases in class I and II, presumably due to IFN-gamma release, which was inhibited by cyclosporine or by mAb against IFN-gamma. The effect of polyI:C was largely simulated by rIFN-alpha, whereas the effect of allogeneic cells was simulated by rIFN-gamma. Thus, rIFN-alpha and its inducers in vivo produce a sustained increase in renal class I expression in kidney and other tissues, sometimes with changes in class II expression. Such effects could be relevant to the immune modulatory actions of IFN, and to the immunologic consequences of viral infections.
Halloran
P F
PF
Department of Medicine, University of Alberta, Edmonton, Canada.
Urmson
J
J
Van der Meide
P H
PH
Autenried
P
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D009980:Influenza A virus / Q000276:immunology; D007369:Interferon Inducers / Q000008:administration & dosage*; D007370:Interferon Type I / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology; D007668:Kidney / Q000032:analysis / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009928:Organ Specificity / Q000187:drug effects; D011070:Poly I-C / Q000008:administration & dosage; D011994:Recombinant Proteins; D013045:Species Specificity / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007369:Interferon Inducers; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D011070:Poly I-C