Specific prolongation of MHC class II disparate skin allografts by in vivo administration of anti-IFN-gamma monoclonal antibody.
In vivo rejection of MHC class II disparate skin allografts has been thought to involve IFN-gamma-induced expression of MHC class II alloantigens because less than 3% of skin epidermal cells express MHC class II alloantigens constitutively. In our study we directly tested this hypothesis by examining the effect of in vivo administered anti-IFN-gamma mAb on rejection of MHC class II disparate skin allografts, and comparing its effect on rejection of MHC class I disparate skin allografts placed on the same individual mice. We found that anti-IFN-gamma mAb blocked the rejection of MHC class II disparate skin allografts, but had no effect on the rejection of MHC class I disparate skin allografts. These results demonstrate that endogenously produced IFN-gamma is critical for rejection of MHC class II disparate skin allografts, but not for rejection of MHC class I disparate skin allografts. Thus, this study strongly supports the concept that MHC class II rejection responses require IFN-gamma induced MHC class II expression on keratinocytes of the allograft.
Rosenberg
A S
AS
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892.
Finbloom
D S
DS
Maniero
T G
TG
Van der Meide
P H
PH
Singer
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D006085:Graft Survival; D006183:H-2 Antigens / Q000276:immunology; D006648:Histocompatibility; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma