Immunosuppressive Effects of Total Lymphoid Irradiation on Kidey Transplantation

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1) WE REPORTED PROLONGATION OF SKIN ALLOGRAFTS IN DOGS BY A COMBINED TREATMENT OF PREOPERATIVE FRACTIONATED LYMPHOID IRRADIATION(FLI), 150RAD/DAY FOR 5 DAYS, Ia-POSITIVE DONOR-SPECIFIC BONE MARROW( <Ia^+> DSBM)CELL INFUSION AT THE TIME OF SKIN GRAFTING, AND SHORT-TERM(3WEEKS) POSTOPERATIVE ADMINISTRATION OF AZATHIOprine(AZA). PREOPERATIVE TREATMENT WITH FLI ALONE, POSTOPERATIVE AZA ALONE, OR BOTH WERE NOT EFFECTIVE IN THE PROLONGATION OF SKIN ALLOGRAFTS.(TRANSPLANT. PROC. 17:830, 1985).2) THEN, WE EXAMINED WHETHER OR NOT THIS TREATMENT IS ALSO APPLICABLE TO THE PROLONGATION OF KIDNEY ALLOGRAFTS IN DOGS.3) TO OBTAIN REPRODUCIBLE PROLONGATION OF KIDNEY ALLOGRAFTS FOR >30 DAYS, 1500RAD (1500RAD/DAY FOR 10DAYS) OF PREOPERATIVE FLI, AND 3-MONTH ADMINISTRATION OF AZA(1MG/KG/DAY) WERE NECESSARY, APART FROM <Ia^+> DSBM CELL INFUSION.4) NO PROLONGATION OF THE GRAFTS WAS SEEN IN CYCLOSPORINE(CYA)-TREATED DOGS IN STEAD OF AZA WITH THE DOSE OF 10MG/KG/DAY. COMBINED WITH THE PRETREATMENT OF FLI AND <Ia^+> DSBM CELL INFUSION, HOWEVER, CYA HAD A SYNERGISTIC EFFECT ON THE PROLONGATION OF KIDNEY GRAFTS FROM BONE MARROW DONORS, AS SEEN IN AZA TREATED DOGS. ONE DOG HAS RETAINED THE GRAFT FROM BONE MARROW DONOR FOR > 200 DAYS, WITH CESSATION OF CYA AT DAY 90.5) FROM APPEARANCE OF SIDE EFFECTS AFTER TREATMENT, THE DEGREE OF BONE MARROW SUPPRESSION WAS QUITE SLIGHT IN ALL GROUP, HOWEVER, THE FREQUENCY OF PLATELET DECREASE WAS MORE COMMON IN AZA-TREATED GROUP. MOREOVER, THE DEGREE OF LIVER DYSFUNCTION WAS HIGER IN AZA-TREATED GROUP THAN IN THE CYA TREATED GROUP. (TRANSPL.PROC. IN PRESS). CYA MAY BE SUPERIOR TO AZA AS AN ADJUVANT THERAPY IN THESE EXPERIMENT: HOWEVER, THE OPTIMAL DOSE OR TERM OF ADMINISTRATION ARE STILL UNKNOWN, ESPECIALLY IN INDUCING IMMUNOLOGICAL UNRESPONSIVENESS, WITH SPECIAL REFERENCE TO THE PROPER DOSE OR DURATION OF IRRADIATION.