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.
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.
Bos
G M
GM
Department of Immunology, University of Limburg, The Netherlands.
Majoor
G D
GD
van Breda Vriesman
P J
PJ
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D016026:Bone Marrow Transplantation; D003524:Cyclosporins / Q000097:blood / Q000633:toxicity*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007958:Leukocyte Count; D051381:Rats; D011917:Rats, Inbred Lew; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014916:Whole-Body Irradiation
D003524:Cyclosporins