Scintigraphic imaging of MHC class II antigen induction in mouse kidney allografts: a new approach to noninvasive detection of early rejection.
Mice with kidney transplants were investigated to determine whether early kidney allograft rejection could be detected by radioimmune scintigraphy targeting major histocompatibility complex (MHC) class II antigens induced on donor organ cells. Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients. Each mouse was injected intravenously with 100 microCi of 123I-labeled anti-MHC class II monoclonal antibody (mAb; Y17, anti-IEk) 16 h before scintigraphy. After imaging, mice were sacrificed for tissue counting and histopathological examination. Radiotracer uptake in the nontreated allografts increased starting on the 3rd day after transplantation, peaked at around the 6th day, and then gradually decreased. Rejecting allografts with only focal perivascular mononuclear cell infiltration could be identified by scintigraphy. However, allografted mice without evidence of rejection and isografted mice did not show an increase in radiotracer uptake. Rejecting BALB/c kidney transplanted into C3H/He mice did not show an increase in Y17 mAb uptake, suggesting that class II antigens induced on donor kidneys are solely responsible for the mAb uptake in positive scintigrams of rejecting allografts. Five allografted mice were treated with anti-CD3 mAb and cyclosporin starting 3-9 days after transplantation. Radiotracer uptake decreased after 4 weeks of treatment and increased 2 weeks after the cessation of immunosuppressive treatment, reflecting suppression and recurrence of rejection, as determined by histological examination. These changes could be followed scintigraphically. We conclude that changes in class II antigen expression can be assessed by the 123I-labeled anti-MHC class II antigen mAb and that it is a sensitive and noninvasive method for detecting kidney allograft rejection.
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Cardiac Unit, Massachusetts General Hospital, Boston 02114.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D016030:Kidney Transplantation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011877:Radionuclide Imaging; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007457:Iodine Radioisotopes