Cyclosporin A induces a selective, reversible suppression of T-helper lymphocyte regeneration after syngeneic bone marrow transplantation: association with syngeneic graft-versus-host disease in rats

Abstract

Experimental studies in rats have established that a combination of lethal X-irradiation, syngeneic bone marrow transplantation (sBMT) and temporary administration of Cyclosporin A (CyA) leads to the development of a disease defined as syngeneic graft-versus-host disease or CyA-induced autoimmunity. This study demonstrates that the combination of lethal X-irradiation, sBMT, and CyA selectively suppresses the repopulation of T-helper cells, as monitored in peripheral blood. The suppression of T-helper cell regeneration is maintained as long as CyA is administered. In addition, development of CyA-induced autoimmunity does not start as long as CyA is given. After withdrawal of CyA T-helper cells recover. Their reappearance in the peripheral circulation coincides with the development of syngeneic graft-versus-host disease, suggesting a role of these cells in initiating or causing the disease.