Jenkins M, Mills J, Kohl S
Department of Pediatrics, San Francisco General Hospital Medical Center, University of California 94110.
Pediatr Res. 1993 May;33(5):469-74. doi: 10.1203/00006450-199305000-00010.
In infants born to mothers infected with the human immunodeficiency virus (HIV), antibody-dependent cellular cytotoxicity (ADCC) or natural killer cytotoxicity (NKC) may either eliminate infection or ameliorate its course. We developed and standardized an assay for cytotoxicity of HIV-infected cells and studied the capacity of leukocytes from healthy neonates and adults to lyse HIV-infected cells by ADCC and NKC. The chosen target cell line, a T cell line infected with the HXB-2 clone of human T-cell lymphotrophic virus-IIIB, displayed stable surface expression of viral antigens over months of continuous culture and allowed simultaneous assessment of NKC and ADCC of effector cell populations. Conditions for optimal ADCC lysis of target cells were defined for unpurified peripheral blood mononuclear cells and purified lymphocytes and monocytes. Polymorphonuclear neutrophils from healthy adults and neonates exhibited low activity in ADCC of HIV-infected targets. Lymphocytes and monocytes from adults were found to differ in antibody dependence, kinetics, and sensitivity to latex inhibition for ADCC-mediated lysis of HIV-infected targets. Peripheral blood mononuclear cells of healthy neonates and adults displayed equivalent capacity to mediate NKC of HIV-infected targets. However, neonates' peripheral blood mononuclear cells were found to be significantly less active than adults' in ADCC lysis of HIV-infected cells. This pattern of diminished ADCC cytotoxicity with intact NKC is the opposite of that seen in HIV-infected adults. Our findings suggest that therapies designed to enhance ADCC effector cell function in the neonate may help interrupt vertical transmission of HIV.
在感染人类免疫缺陷病毒（HIV）的母亲所生的婴儿中，抗体依赖性细胞毒性（ADCC）或自然杀伤细胞毒性（NKC）可能会消除感染或改善其病程。我们开发并标准化了一种针对HIV感染细胞的细胞毒性检测方法，并研究了健康新生儿和成年人的白细胞通过ADCC和NKC裂解HIV感染细胞的能力。所选择的靶细胞系是一种感染了人类T细胞白血病病毒IIIB型HXB - 2克隆的T细胞系，在连续培养数月的过程中病毒抗原在其表面稳定表达，从而能够同时评估效应细胞群体的NKC和ADCC。确定了未纯化的外周血单核细胞以及纯化的淋巴细胞和单核细胞对靶细胞进行最佳ADCC裂解的条件。健康成年人和新生儿的多形核中性粒细胞在HIV感染靶细胞的ADCC中活性较低。发现成年人的淋巴细胞和单核细胞在抗体依赖性、动力学以及对ADCC介导的HIV感染靶细胞裂解的乳胶抑制敏感性方面存在差异。健康新生儿和成年人的外周血单核细胞在介导HIV感染靶细胞的NKC方面表现出同等能力。然而，在HIV感染细胞的ADCC裂解中，发现新生儿的外周血单核细胞活性明显低于成年人。这种NKC完整但ADCC细胞毒性降低的模式与HIV感染成年人的情况相反。我们的研究结果表明，旨在增强新生儿ADCC效应细胞功能的疗法可能有助于阻断HIV的垂直传播。
