A requirement for continued graft presence in the maintenance of systemic tolerance induced by cyclosporin A (CyA) in rats.
We report on a requirement for the continued presence of a heart graft in the maintenance of systemic tolerance induced by cyclosporin A (CyA). Hearts from DA rats (RT1a) were grafted into PVG (RT1c) recipient. CyA-induced long-term survivors (LTS) bearing functioning heart grafts are systemically tolerant, as demonstrated by the significant prolongation (greater than 50 days) of donor-strain skin grafts. In contrast, donor-strain skins grafted 3 weeks after the removal of heart grafts from LTS are acutely rejected (median survival 10.0 days; P less than 0.005). Using an adoptive transfer assay, 5 x 10(7) splenic lymphocytes obtained from LTS 3 weeks after the removal of the heart grafts fail to mediate adoptive tolerance (median survival 17.0 days), in contrast to the tolerance achieved by splenic lymphocytes obtained from LTS with functioning heart grafts (median survival greater than 100 days; P less than 0.005).
Lim
S M
SM
Department of Surgery, Addenbrooke's Hospital, Cambridge, UK.
White
D J
DJ
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival; D016027:Heart Transplantation; D007108:Immune Tolerance; D008297:Male; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D003524:Cyclosporins