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 ea rly kidney allograft rejection could be detected by radioimmune scinti graphy targeting major histocompatibility complex (MHC) class II antig ens induced on donor organ cells. Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients. Each mouse was injecte d intravenously with 100 muCi of I-123-labeled anti-MHC class II monoc lonal antibody (mAb; Y17, anti-IE(k)) 16 h before scintigraphy. After imaging, mice were sacrificed for tissue counting and histopathologica l examination. Radiotracer uptake in the nontreated allografts increas ed 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 rejecti on 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 positiv e scintigrams of rejecting allografts. Five allografted mice were trea ted with anti-CD3 mAb and cyclosporin starting 3-9 days after transpla ntation. Radiotracer uptake decreased after 4 weeks of treatment and i ncreased 2 weeks after the cessation of immunosuppressive treatment, r eflecting suppression and recurrence of rejection, as determined by hi stological examination. These changes could be followed scintigraphica lly. We conclude that changes in class II antigen expression can be as sessed by the I-123-labeled anti-MHC class II antigen mAb and that it is a sensitive and noninvasive method for detecting kidney allograft r ejection.