Bugelski P J, Thiem P A, Truneh A, Morgan D G
Department of Experimental Pathology, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania 19406.
Toxicol Pathol. 1991;19(4 Pt 2):580-8. doi: 10.1177/019262339101900403.
Recombinant soluble CD4 (sT4) has been shown to inhibit infectivity of HIV. Because of the role CD4 plays in the interaction of T-helper lymphocytes and cells bearing MHC Class II antigens, a potential adverse effect of therapy with sT4 is interference with lymphocyte function. To address this issue, we studied the effects of sT4 on mitogen-mediated blastogenesis, mixed lymphocyte reactions, and delayed type hypersensitivity reactions (DTH) in cynomolgus monkeys. We found no evidence of sT4-mediated suppression on the in vitro response to concanavalin A, phytohemagglutinin or pokeweed mitogen in 2-way mixed lymphocyte reactions, either when sT4 was added to the cultures or when cells were obtained 3 hr after drug administration from animals that received up to 100 mg/kg as an intravenous bolus. Furthermore, we also found no effect of sT4 on lymphocyte subsets or on the ability of monkeys to respond to dinitrochlorobenzene (DNCB)-mediated DTH. Because of the high degree of conservation of CD4 and MHC Class II antigens across the macaque-human barrier, these data suggest that soluble CD4-like molecules are unlikely to be immunosuppressive in humans.
重组可溶性CD4（sT4）已被证明可抑制HIV的感染性。由于CD4在辅助性T淋巴细胞与携带MHC II类抗原的细胞相互作用中所起的作用，sT4治疗的一个潜在不良反应是干扰淋巴细胞功能。为解决这一问题，我们研究了sT4对食蟹猴有丝分裂原介导的细胞增殖、混合淋巴细胞反应和迟发型超敏反应（DTH）的影响。我们发现，无论是将sT4添加到培养物中，还是在静脉推注高达100 mg/kg药物后3小时从动物获取细胞，在双向混合淋巴细胞反应中，均未发现sT4介导的对刀豆蛋白A、植物血凝素或商陆有丝分裂原体外反应的抑制作用。此外，我们还发现sT4对淋巴细胞亚群或猴子对二硝基氯苯（DNCB）介导的DTH反应能力没有影响。由于CD4和MHC II类抗原在猕猴-人类屏障间具有高度保守性，这些数据表明可溶性CD4样分子在人类中不太可能具有免疫抑制作用。
