Immunosuppressive Effects of Total Lymphoid Irradiation on Kidey Transplantation

1)我们报道了通过术前分级淋巴细胞照射（FLI）， 150RAD/天，持续5天，植皮时输注Ia阳性供体特异性骨髓（<Ia^+> DSBM）细胞和术后短期（3周）给予硫唑嘌呤（AZA）的联合治疗延长狗的同种异体皮肤移植。术前单独使用fli，术后单独使用aza，或两者都不能有效延长同种异体皮肤移植的时间。程序17:830,1985)。2)然后，我们检查了这种治疗是否也适用于延长狗的同种异体肾移植时间。3)为了获得可重复延长的同种异体肾移植时间，术前FLI 1500RAD （1500RAD/天，10天）和3个月的AZA（1MG/KG/天）治疗是必要的，除了<Ia^+> DSBM细胞输注外。4)在环孢素（CYA）治疗的狗中没有看到移植时间延长，而不是10MG/KG/天的AZA。然而，与FLI预处理和<Ia^+> DSBM细胞输注相结合，CYA对延长骨髓供者肾移植具有协同作用，正如在AZA治疗的狗身上看到的那样。1只犬骨髓供体移植体留置100 ~ 200天，治疗后出现副作用90.5天停用cya，各组骨髓抑制程度均较轻，但血小板减少频率以aza组多见。此外，aza治疗组的肝功能障碍程度高于cya治疗组。(TRANSPL.PROC。在出版社)。在这些实验中，Cya作为辅助治疗可能优于aza，然而，最佳剂量或给药期限仍然未知，特别是在诱导免疫无反应性方面，特别涉及适当的剂量或照射时间。

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.