Induced tolerance to cardiac allografts with multiple intravenous injection of donor spleen cells

Abstract

To study the methods and mechanisms of immune tolerance in cardiac transplantation. Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: untreated, intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat, intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide, 11 days later heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR), the role of interleukin-2 (IL-2) to MLR and the role of tolerant rat splenocytes to MLR were measured after operation. The survival time of heart allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide [MST: (85.3 +/- 7.5) d, t = 0, P < 0.01] was significantly longer than in the groups of untreated [MST: (7.3 +/- 1.0) d], intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat [MST: (7.9 +/- 0.9) d], intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (8.1 +/- 1.2) d], intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (25.8 +/- 3.5) d]. Only a few inflammatory cells infiltrated in cardiac allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide. MLR in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide were significantly decreased compared with those of normal control (t = 0, P < 0.01). IL-2 could partly reversed the hyporesponsiveness of MLR in tolerant rats, the tolerance could be transferred in vitro. Multiple injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide to recipients could induce immune tolerance to cardiac allografts.