Syngeneic or autologous graft-versus-host disease

Graft-versus-host disease (GVHD) until recently was supposed to occur only when immunocompetent T lymphocytes are infused into immunoincompetent allogeneic hosts that possess histocompatibility antigens not possessed by the donor that could act as targets for cell-mediated cytotoxicity. A syndrome clinically and histologically identical to mild allogeneic GVHD occurs infrequently, following syngeneic or autologous bone marrow transplantation (BMT). This syndrome called syngeneic or autologous GVHD can be regularly produced with Cyclosporine (CsA) in animals undergoing syngeneic or autologous BMT. Animals with this syndrome develop T cells that are autocytotoxic to Ia antigen-bearing cells. The presence of an irradiated thymus and CsA administration is necessary to produce this disease. Operationally, this disease results from a disturbance of balance between a normally present autoregulatory cell and an autocytotoxic T cell. The study of mechanisms involved in the generation of this disease will add to our fundamental understanding of the cellular regulation of autocytotoxic T cell-medicated reactions and diseases. Most recently, we have been able to induce this disease in man with the aim of investigating its therapeutic effect in autologous BMT in patients with Ia-bearing tumors.