Immunosuppressive Effects of Total Lymphoid Irradiation on Kidey Transplantation

1)我们报道了一种联合治疗的方法，即术前分次淋巴照射（FLI），150拉德/天，持续5天，皮肤移植时输注Ia阳性供体特异性骨髓（<Ia^+> DSBM）细胞，术后短期（3周）给予硫唑嘌呤（AZA）。术前单独使用FLI、术后单独使用AZA或两者联合使用对同种异体皮肤移植物的延长没有明显效果。（移植。第十七章：830，1985）。2）然后，我们探讨了这种治疗方法是否也适用于犬同种异体肾移植的延长。3）获得可繁殖的肾延长Y同种异体移植物>30天，1500 RAD（1500 RAD/天，持续10天）术前FLI和3个月AZA给药（1 mg/KG/天）是必要的，除<Ia^+> DSBM细胞输注外。4）环孢菌素未观察到移植物延长（CYA）给药犬代替AZA，剂量为10 mg/KG/天。与FLI和<Ia^+> DSBM细胞输注预处理相结合，CyA对AZA处理的狗移植肾的延长有协同作用。一只犬从骨髓供体处保留移植物超过200天，在第90.5天CyA停止。从治疗后出现的副作用来看，所有组中骨髓抑制的程度都很轻，但AZA治疗组中血小板减少的频率更常见。AZA治疗组肝功能损害程度明显高于CYA治疗组。（翻译，出版中）。在这些实验中，作为辅助治疗，CYA可能上级AZA：然而，最佳剂量或给药时间仍然未知，特别是在诱导免疫无反应方面，特别是关于适当的照射剂量或照射持续时间。

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.