Correlation Between Class Ii Antigen (Dr) Expression and Interleukin-2-Induced Lymphocyte Proliferation During Acute Cardiac Allograft Rejection

We have previously reported a correlation between biopsy-proven rejection and the presence of IL-2-responsive lymphocytes for biopsy specimens from human cardiac allografts. We thus hypothesized a relationship between tissue expression of HLA class II antigen (DR) and the outgrowth of IL-2-responsive lymphocytes. Employing immunofluorescence DR staining with a propidium iodide counterstain in consecutive specimens from 41 patients, we found two patterns of DR expression: DR expressed on the vascular endothelial surface (donor antigens) and/or on myocardial infiltrating cells (presumably recipient antigens). Specimens were categorized by histologic diagnosis as "baseline nonrejecting controls" that were obtained 7.5 +/- 0.4 (mean +/- SE) days posttransplantation, "nonrejecting" (obtained 59.9 +/- 5.8 days posttransplantation), "prerejecting" (obtained 47.7 +/- 6.3 days posttransplantation), and "rejecting" (obtained 101.3 +/- 10.1 days posttransplantation). Prerejecting specimens were histologically negative specimens obtained from patients a mean of 6.0 +/- 0.4 days before a biopsy-proven rejection episode. The percentage of specimens positive for interstitial DR staining were: less than 1% for controls, 30% for nonrejecting specimens, 68% for prerejecting, and 46% for rejecting. For vascular DR staining, 25% of control specimens were positive, 56% of nonrejecting, 74% of prerejecting, and 73% of rejecting specimens. Culture positivity was seen for 38% of controls, 35% of nonrejecting specimens, 79% of prerejecting, and 70% of rejecting. Vascular DR staining was higher than interstitial staining for all specimen categories. For the vascular pattern, the mean score was significantly higher for culture-positive specimens compared to culture negative (0.87 +/- 0.1 vs. 0.59 +/- 0.1; P less than 0.01). A similar relationship was not found for the interstitial pattern. Lymphocyte growth occurred in conjunction with vascular DR upregulation significantly more frequently than in conjunction with interstitial DR expression (65% vs. 35% of culture-positive specimens, P less than 0.0001). These findings suggest a relationship between DR expression, lymphocyte growth, and acute rejection. Vascular DR and interstitial DR patterns show several differences with respect to kinetics of expression and correlation with histology and culture, and thus may represent different processes.