The influence of the pattern of inflammation and administration of steroids on class II MHC antigen expression in renal transplants.
We have investigated the expression of class II major histocompatibility complex (MHC) antigens in human renal allografts before, during, and after the first episode(s) of rejection, and correlated the antigen expression with the cytological pattern of inflammation as well as with the extent of steroid administration. The results confirm that the class II MHC antigens are rapidly lost from a renal transplant after successful transplantation. Downregulation of graft class II antigenicity was observed in all three immunosuppressive regimens employed, with a steroid dose ranging from 0.5 +/- 0.2 mg/kg/day to 1.8 +/- 0.3 mg/kg/day of methylprednisolone. During rejection the class II MHC antigens reappear in the graft parenchymal (vascular endothelial and tubular) cells, whereas after the successfully treated episode they again disappear from the graft. The upregulation of graft antigenicity is associated only with inflammatory patterns with a distinct blastogenic component; nonblastogenic patterns of inflammation are not associated with upregulation of class II antigens. During blastogenic inflammation, the extent of class II antigen expression was inversely proportional to the amount of steroid administered. The results support the suggestion that upregulation of class II antigen contents in a graft is due to (gamma-interferon released by) the inflammatory (T) blast cells, and suggest that a major downregulating mechanism of class II antigen expression is administration of glucocorticosteroids.
D005938:Glucocorticoids / Q000494:pharmacology*; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D009393:Nephritis / Q000276:immunology*
D005938:Glucocorticoids; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007371:Interferon-gamma