De Fazio S R, Masli S, Gozzo J J
Department of Pharmaceutical Science, Bouvé College of Pharmacy and Health Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Transplantation. 1996 Jan 15;61(1):104-10. doi: 10.1097/00007890-199601150-00021.
Allograft unresponsiveness can be induced by donor bone marrow cells (BMC) in antilymphocyte serum (ALS)-treated recipients. The effect of administering monoclonal anti-CD4 and -CD8 at several points has been examined in a mouse skin allograft model of this protocol. Brief peritransplant administration of anti-CD4 and -CD8 was used to replace ALS. Anti-CD4 treatment prolonged graft survival only slightly and conditioned recipients poorly for the effect of posttransplantation donor BMC infusion. Anti-CD8 was ineffective in both capacities. A mixture of anti-CD4 and anti-CD8 was at least as effective as ALS in prolonging graft survival and in promoting the beneficial effects of donor BMC. Like the monoclonal antibodies, ALS also depleted splenic and lymph node CD4+ and CD8+ cells. Injection of ALS, but not the monoclonal antibodies, altered the CD4/CD8 phenotype of thymocytes, although persistent binding of both types of antibody to thymocytes was demonstrated. Abrogation of the positive effect of BMC by reconstitution of normal spleen cells on day +3 after ALS treatment confirmed that cell depletion is a requirement of this system. Monoclonal antibodies were also given to ALS/BMC-treated recipients after their grafts had become established. Anti-CD8 injection at either 2 or 4 weeks after transplantation further prolonged graft survival. In contrast, anti-CD4 injection at 2 or 6 weeks after grafting precipitated rejection, which suggests that continued allograft survival following ALS and donor BMC treatment is due to the activity of a CD4+ cell population.
在接受抗淋巴细胞血清（ALS）治疗的受体中，供体骨髓细胞（BMC）可诱导同种异体移植无反应性。在该方案的小鼠皮肤同种异体移植模型中，已研究了在几个时间点给予单克隆抗CD4和抗CD8的效果。在移植前后短暂给予抗CD4和抗CD8以替代ALS。抗CD4治疗仅略微延长了移植物存活时间，并且对移植后供体BMC输注的效果预处理受体不佳。抗CD8在这两方面均无效。抗CD4和抗CD8的混合物在延长移植物存活时间和促进供体BMC的有益作用方面至少与ALS一样有效。与单克隆抗体一样，ALS也消耗了脾脏和淋巴结中的CD4 +和CD8 +细胞。注射ALS而非单克隆抗体改变了胸腺细胞的CD4/CD8表型，尽管已证明两种类型的抗体均与胸腺细胞持续结合。在ALS治疗后第+3天通过重建正常脾细胞消除BMC的阳性作用，证实细胞耗竭是该系统的必要条件。在移植物建立后，也将单克隆抗体给予接受ALS/BMC治疗的受体。移植后2周或4周注射抗CD8可进一步延长移植物存活时间。相比之下，移植后2周或6周注射抗CD4会加速排斥反应，这表明ALS和供体BMC治疗后同种异体移植物的持续存活归因于CD4 +细胞群体的活性。
