Essential initial immunostimulation in graft coronary arteriosclerosis induction detected by retransplantation technique in rats: The participation of T cell subsets

Graft coronary arteriosclerosis occurs as chronic rejection after heart transplantation. In the previous studies, we have examined the minimum period of allogeneic stimulation to induce this change, using heterotopic rat heart transplantation and a retransplantation model. Retransplantation of allografts back into the donor strain did not prevent graft arteriosclerosis if the grafts had resided in the primary recipient for up to five days. In this study, the participation of the T cell subset causing graft coronary arteriosclerotic change was assessed using the same model. The transplanted rats in fully allogeneic or non-MHC antigen mismatch combinations were treated with a short-course administration of FK506. The graft was removed and retransplanted into the donor strain rats to escape from further immunological stimulation. CD4(+) T cells and/or CD8(+) T cells of first recipient rats in both combinations were eliminated by monoclonal antibodies. The grade of arteriosclerosis in the retransplanted hearts was evaluated on a basis of a scale from 0-4 according to the histological appearance of the vessel injury on day 40 after initial engraftment. While neither anti-CD4 nor anti-CD8 monoclonal antibody alone had little effect, the administration of both mAbs reduced this arteriosclerotic change and development. In conclusion, the T cell subsets,CD4(+) T cell and CD8(+) T cell play a certain role in the induction of the graft coronary arteriosclerotic change.