Prolongation of skin graft survival across different genetic barriers in rats with cyclosporine--and its potentiation by Bordetella pertussis vaccine.
Skin allografting was performed in rats treated with cyclosporine using strain combinations that differed across the RT1.A (class I) or RT1.B (class II) loci of the major histocompatibility complex (MHC) or across non-MHC loci. Injection of cyclosporine (20 mg/kg) for 14 consecutive days was followed by prolonged acceptance (MST = 67 days) of the skin allografts. Bordetella pertussis vaccine potentiated the effect of cyclosporine, and the synergistic effect of the vaccine occurred only when it was given before grafting. The cyclosporine given for 14 days with or without B pertussis failed to prolong second-set skin grafts. Production of hemagglutinating antibodies in cyclosporine-treated animals was completely suppressed when the skin grafts were in place, and it occurred to a much lesser extent following rejection, as compared with untreated animals. The cyclosporine did not, however, influence the antibody response following second set skin graft rejection. A system in which rats were treated for only 6 days with cyclosporine was developed in order to test the effects of disparities at different histocompatibility loci on the response to cyclosporine, because this regimen gave a marginal, but significant, prolongation of skin grafts across a full RT1 (MHC) difference. There was a differential effect of cyclosporine treatment depending upon the genetic differences involved: a skin graft across an RT1.A (class I) difference was indefinitely prolonged, one across an RT1.B (class II) or RT1.AB difference was slightly prolonged (9 to 12 days and 12.5 to 16.5 days, respectively) and a graft across non-MHC differences was not affected. Hence, the immunosuppressive effects of cyclosporine on skin graft rejection appear to depend upon the genetic disparities between donor and recipient. Exploitation of this finding may lead to the design of more effective, multidrug protocols for the treatment of rejection that would have fewer deleterious side-effects.
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D006386:Hemagglutination Tests; D008285:Major Histocompatibility Complex; D008912:Minor Histocompatibility Loci; D010567:Pertussis Vaccine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016038:Skin Transplantation
D003524:Cyclosporins; D010567:Pertussis Vaccine