Prolongation of cardiac allograft survival by intraportal injection of donor antigens--differential mechanisms according to the timing of injection.

Recently, we reported that intraportal (IP) injection of donor spleen cells (SPCs) before transplantation as well as at the time of transplantation significantly prolongs cardiac allograft survival in rats (7). Long-term establishment of chimerism induced by intraportal administration of SPCs could be a part of this prolongation. In this study, we examined the effect of irradiation of SPCs as a source of donor antigens on cardiac allograft survival. Experiments were carried out using DA (RT1a) as the donor and BUF (RT1b) as the recipient strain. Fifty million irradiated or nonirradiated SPCs were injected either intravenously (i.v.) or intraportally (i.p.) on day -10 or day 0, the day of cardiac allografting. Untreated animals rejected allografts within a mean survival time (MST) of 7.2 +/- 0.8 days (n = 5). Injection (i.p.) of SPCs on both day -10 (n = 4) and day 0 (n = 6) induced significant prolongation of MST over the control (19.0 +/- 4.7, 14.2 +/- 2.1 days; p < 0.001 vs. control), while i.v. injection of SPCs on either day -10 (n = 4) or day 0 (n = 4) failed to do so (9.2 +/- 1.0, 8.5 +/- 0.6 days). Significant prolongation was still observed when irradiated SPCs were injected on day -10 (n = 4; MST: 19.0 +/- 5.4 days, p < 0.002 vs. control), but not when injected on day 0 (n = 5; MST: 9.4 +/- 2.1 days). These data suggest that the immunosuppressive effect of i.p. injection of donor SPCs could be induced by differential mechanisms according to the timing of inoculation of donor antigens.