Transfer of specific unresponsiveness to organ allografts by thymocytes. Specific unresponsiveness by thymocyte transfer.
Prolonged survival of vascularized organ allografts has been produced in unmodified inbred rats by transfer of thymocytes from enhanced, engrafted, syngeneic animals. For these thymocytes to increase significantly the survival of test allografts they must be harvested 6-9 d after transplantation. Thymectomy of the enhanced, engrafted animals during the same critical period causes acute rejection of othewise long surviving grafts. For optimal effect, the enhanced thymocyte donor must be actively and passively immunized and receive a cardiac allograft. The necessity for erythrocytes in the initial active immunization regimen is noted. Additionally, the antigenic specificity of the suppressor effect has been established with two histoincompatible donor rat strains. Cellular and humoral host responses mounted by test graft recipients after thymocyte transfer from enhanced, engrafted donors are different from those mounted either by unmodifed animals acutely rejecting their grafts or by enhanced rats bearing well-functioning grafts. Numbers of T lymphocytes are reduced in the grafted hearts and in the spleens of test graft recipients, a finding paralleled by the complete absence of specific direct lymphocyte-mediated cytotoxicity. In contrast, cytotoxic antibody production, although delayed, is increased in magnitude, peaking around the time of graft rejection. These studies provide evidence that different biological manipulations can modify separate pathways in the complex cellular and humoral responses towards organ allografts. They demonstrate that cellular immunity is critically involved in immunological enhancement of vascularized organ allografts, a phenomenon hitherto considered primarily humoral. It seems clear that cells with suppressor activity are present within the thymus during the early phases of immunological enhancement.