Wee S L, Stroka D M, Preffer F I, Jolliffe L K, Colvin R B, Cosimi A B
Transplantation Unit, Massachusetts General Hospital, Boston 02214.
Transplantation. 1992 Mar;53(3):501-7. doi: 10.1097/00007890-199203000-00001.
Significant differences in cellular responses were found among allograft recipients treated with various OKT4A mAb protocols. Recipients of multiple infusion low-dose and 2-bolus OKT4A immunosuppressive regimens regularly showed potent donor-specific cytotoxic CD8+ and CD4+ intragraft T cells and donor-reactive PBMC in MLC tests. In contrast, PBMC isolated from recipients of high-dose OKT4A therapy generally showed very weak or no response to donor-antigens during the later posttransplant periods. Furthermore, an absence of IL2-responsive intragraft cells was found to correlate with stable graft function in these recipients. We conclude that OKT4A mAb, in high doses, can block allosensitization and induce donor-specific nonresponsiveness in vivo. An OKT4A-based therapy, therefore, may have the potential of inducing long-lasting donor-specific immunosuppression, or even tolerance.
在用不同的OKT4A单克隆抗体方案治疗的同种异体移植受者中发现了细胞反应的显著差异。多次输注低剂量和2次推注OKT4A免疫抑制方案的受者在混合淋巴细胞培养试验中经常显示出有效的供体特异性细胞毒性CD8+和CD4+移植内T细胞以及供体反应性外周血单个核细胞。相比之下,在移植后期,从高剂量OKT4A治疗的受者中分离出的外周血单个核细胞通常对供体抗原显示出非常弱的反应或无反应。此外,发现这些受者中缺乏白细胞介素2反应性移植内细胞与移植功能稳定相关。我们得出结论,高剂量的OKT4A单克隆抗体可以阻断同种异体致敏并在体内诱导供体特异性无反应性。因此,基于OKT4A的治疗可能具有诱导持久的供体特异性免疫抑制甚至耐受的潜力。