Mechanism of defective NK cell activity in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. II. Normal antibody-dependent cellular cytotoxicity (ADCC) mediated by effector cells defective in natural killer (NK) cytotoxicity.
Mechanism of defective NK cell activity in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. II. Normal antibody-dependent cellular cytotoxicity (ADCC) mediated by effector cells defective in natural killer (NK) cytotoxicity.
复制标题
获得性免疫缺陷综合症（艾滋病）和艾滋病相关综合症患者的 NK 细胞活性缺陷机制。
作者：
J. Katz;R. Mitsuyasu;M. Gottlieb;L. Lebow;B. Bonavida
我们的研究和其他研究表明，NK效应细胞也可以通过使用NK细胞膜上的Fc γ受体介导抗体依赖性细胞毒性（ADCC）。来自获得性免疫缺陷综合征（AIDS）和AIDS相关复合物患者的外周血淋巴细胞（PBL）表现出较差的NK活性，这是由于NK溶解途径致命打击阶段激活所需的“触发”缺陷所致。因此，阐明艾滋病NK细胞的缺陷是否影响ADCC功能是很重要的。通过51cr -释放实验，发现AIDS PBL的ADCC细胞毒活性在正常范围内，尽管没有明显的NK活性。几个实验证实，相同的效应细胞介导NK CMC和ADCC。消耗含Fc γ r的细胞导致ADCC和NK细胞毒性功能的消除。使用单靶和双靶细胞偶联物进行的单细胞分析显示，ADCC效应物、靶偶联物的频率和艾滋病PBL中杀伤细胞的频率与正常对照中的频率相当。然而，当使用NK和ADCC靶点的混合物形成混合的双靶点偶联物时，AIDS效应细胞只裂解结合的ADCC靶点，而正常效应细胞既裂解结合的NK靶点，也裂解ADCC靶点。这些结果清楚地表明，来自AIDS PBL的NK/K效应细胞，NK活性缺陷，在介导ADCC活性方面没有受损。这些发现得到了ADCC靶点而非NK靶点刺激AIDS PBL释放NK细胞毒因子（NK细胞毒因子是NK CMC反应的假定介质）的支持。这些发现表明，艾滋病中的NK/K细胞通常被ADCC活性触发，而不是被NK活性触发。此外，结果表明，在艾滋病NK/K细胞中，溶解机制没有受损。
Our studies and other investigations have shown that NK effector cells can also mediate antibody-dependent cellular cytotoxicity (ADCC) through the use of the Fc gamma receptor on the NK cell membrane. Peripheral blood lymphocytes (PBL) derived from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex exhibit a poor NK activity due to a defective "trigger" required for activation in the lethal hit stage of the NK lytic pathway. Consequently, it was important to delineate whether the defect in AIDS NK cells affected the ADCC function. By using the 51Cr-release assay, the ADCC cytotoxic activity of AIDS PBL was found to be within the normal range, despite the absence of significant NK activity. Several experiments corroborated that the same effector cells mediate both NK CMC and ADCC. Depletion of Fc gamma R-bearing cells resulted in elimination of both the ADCC and NK cytotoxic functions. Single cell analyses, using one- and two-target cell conjugates, revealed that the frequency of ADCC effector:target conjugates and the frequency of killer cells from AIDS PBL were comparable to the frequencies seen in the normal controls. However, when mixtures of NK and ADCC targets were used to form mixed two-target conjugates, the AIDS effector cells lysed only the bound ADCC target, whereas the normal effector cells lysed both the bound NK and ADCC targets. These results demonstrate clearly that the same NK/K effector cells from AIDS PBL, defective in NK activity, are not impaired in mediating ADCC activity. These findings were supported by the demonstration that AIDS PBL stimulated with ADCC targets, but not with NK targets, released NK cytotoxic factors, postulated mediators of the NK CMC reaction. These findings indicate that the NK/K cells in AIDS are triggered normally for ADCC activity but are not triggered for NK activity. Furthermore, the results indicate that the lytic machinery is not impaired in the AIDS NK/K cells.