Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes

C yclosporine (CsA)l is a very potent immunosuppressive agent that has an apparent selective action on T lymphocyte-dependent immune responses (1, 2) . It has been used extensively in clinical transplantation to prevent solid organ allograft rejection and graft-versus-host disease (GVHD) (3, 4) . CsA is currently being evaluated as a therapeutic agent for the treatment ofautoimmune disease, and the results from these trials appear quite promising (5) . Despite its potent immunosuppressive activity, CsA therapy after autologous or syngeneic bone marrow transplantation paradoxically elicits a T cell-mediated autoimmune syndrome with pathology identical to GVHD occurring after allogeneic bone marrow transplantation (BMT) (6) (7) (8) (9) (10) . Hence, this CsA-induced autoimmune syndrome was originally termed syngeneic GVHD (SGVHD) (6) . The immunobiology of SGVHD is complex and is not completely understood, but it appears to be due to the uncoupling of normal immunologic homeostasis involved in self-nonself recognition (11) .