Cyclosporine facilitates chimeric and inhibits nonchimeric tolerance after posttransplant total lymphoid irradiation.
BACKGROUND
Previous studies showed that Lewis rats given posttransplant total lymphoid irradiation, antithymocyte globulin, and a single infusion of ACI peripheral blood or bone marrow cells develop tolerance to ACI heart allografts.


METHODS
To determine the effects of cyclosporine on these tolerance induction protocols, groups of Lewis hosts, given either ACI blood or marrow infusions, were given a 60-day course of daily cyclosporine immediately after the cell infusion.


RESULTS
Cyclosporine treatment was associated with uniform graft rejection in the groups given an ACI blood transfusion, and was associated with uniform graft acceptance in the groups given an ACI bone marrow infusion. Studies of donor-type T and B cell chimerism in the host blood showed that cyclosporine facilitated chimerism in the hosts given ACI bone marrow cells, and stable chimerism over a 300-day observation period was predicted by detectable chimerism by day 30. None of the hosts given ACI blood cells developed chimerism.


CONCLUSIONS
Cyclosporine facilitated long-term graft acceptance in a tolerization protocol that induced mixed chimerism, but prevented long-term graft acceptance in a tolerization protocol that did not induce chimerism.
Lan
F
F
Department of Medicine, Stanford University School of Medicine, California 94305-5111, USA.
Hayamizu
K
K
Strober
S
S
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000276:immunology; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008297:Male; D011836:Radiation Tolerance; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D018183:Transplantation Chimera / Q000187:drug effects*; D014916:Whole-Body Irradiation
D000961:Antilymphocyte Serum; D016572:Cyclosporine