Suzuki T, Sundt T M, Mixon A, Sachs D H
Transplantation Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Transplantation. 1990 Jul;50(1):76-81. doi: 10.1097/00007890-199007000-00014.
The effects of in vivo administration of monoclonal antibodies directed against the two major mature T cell subsets of miniature swine have been examined. Antibody 76-2-11, specific for the porcine CD8 cell-surface antigen, caused elimination of CD8+ T cells from the peripheral lymphocyte pool by 4-6 days following a single intravenous infusion. This depletion persisted while excess antibody was detectable in the serum and CD8+ cells returned rapidly to normal levels following the disappearance of serum antibody. In vitro functional assays performed on PBL during the period of depletion showed no effect on proliferative responses but a profound inhibition of ability to generate CTL. In contrast, administration of monoclonal antibody 74-12-4, specific for CD4+ porcine T lymphocytes, caused no consistent change in the level of CD4+ cells in the peripheral lymphocyte pool. By flow microfluorometry, CD4+ peripheral lymphocytes were found to be coated with the antibody, and there also was excess antibody in the serum for at least 4 days in two of the three animals treated. No effects on in vitro proliferative responses or generation of CTL in vitro were observed, even during the period of excess circulating antibody. Treatment with both antibodies was tolerated well by all animals. These findings are similar to those that have been found in clinical studies of monoclonal antibody treatment and suggest that the pig will provide a large animal preclinical model in which the effects of in vivo treatment with monoclonal antibodies on parameters of transplantation immunity can be tested.
已研究了体内给予针对小型猪两个主要成熟T细胞亚群的单克隆抗体的效果。特异性针对猪CD8细胞表面抗原的抗体76 - 2 - 11，在单次静脉输注后4 - 6天，导致外周淋巴细胞池中CD8⁺T细胞消除。在血清中可检测到过量抗体时，这种耗竭持续存在，且在血清抗体消失后，CD8⁺细胞迅速恢复至正常水平。在耗竭期间对外周血淋巴细胞（PBL）进行的体外功能试验显示，对增殖反应无影响，但对产生细胞毒性T淋巴细胞（CTL）的能力有显著抑制。相比之下，给予特异性针对CD4⁺猪T淋巴细胞的单克隆抗体74 - 12 - 4，未引起外周淋巴细胞池中CD4⁺细胞水平的一致变化。通过流式微荧光术发现，CD4⁺外周淋巴细胞被抗体包被，并且在三只接受治疗的动物中的两只中，血清中至少4天存在过量抗体。即使在循环抗体过量期间，也未观察到对体外增殖反应或体外产生CTL的影响。所有动物对两种抗体治疗的耐受性良好。这些发现与单克隆抗体治疗的临床研究结果相似，表明猪将提供一个大型动物临床前模型，可在其中测试体内用单克隆抗体治疗对移植免疫参数的影响。
