A COMPARISON BETWEEN PANCREAS AND HEART ALLOTRANSPLANTATION AFTER ADMINISTRATION OF DONOR-SPECIFIC ANTIGEN AND CYCLOSPORINE

Abstract

These experiments compared the effect of a five-day course (days - 1 to +3) of cyclosporine therapy coupled with pretransplant (day - 1) administration of donor-specific antigen (whole blood or splenocytes) on either pancreatic or heart allograft survival in the Buffalo to Lewis rat donor-recipient combination. CsA therapy alone significantly (P less than 0.001) prolonged both heart (16.2 +/- 1.6 days) and pancreas (12.5 +/- 1.5 days) graft survival when compared with nonimmunosuppressed control heart and pancreas grafts (7.7 +/- 1.8 and 7.9 +/- 1.0 days, respectively). Pretransplant transfusion with either 2 ml of BUF whole blood or 2 x 10(8) red cell-free splenocytes on day -1 also resulted in a significant (P less than 0.001) prolongation of heart survival (14.0 +/- 1.2 and 14.0 +/- 1.6 days, respectively) but did not improve pancreas allograft survival (9.4 +/- 1.5 and 8.5 +/- 1.0 days, respectively). Combination CsA and antigen therapy further improved heart graft survival to 26.5 +/- 6.1 days (whole blood) and 28.8 +/- 5.8 days (splenocytes) but did not improve pancreas graft survival over that of CsA therapy alone. Extension of CsA therapy by adding two additional 3-day cycles on days 10-12 and 17-19 further improved heart graft survival both after CsA alone (35.2 +/- 3.2 days) and after CsA coupled with whole-blood transfusion (45.3 +/- 8.6 days), but did not have a salutary effect on pancreas allograft survival. Portal vein administration of donor antigen was equally effective as systemic inoculation in prolonging heart graft survival when the splenocytes were given alone (11.6 +/- 1.7 days). Conversely, pancreas allograft survival was not beneficially effected by portal antigen administration whether or not CsA was given. These data demonstrate the ability of pretransplant donor-specific antigen administration and short-term CsA therapy to significantly prolong rat heart allograft survival across a strong MHC histocompatibility barrier-but, surprisingly, they also demonstrate the failure of this regimen to have a salutary effect on pancreas allograft survival.