NK Cell Function and Antibodies Mediating ADCC in HIV-1-Infected Viremic and Controller Patients
NK Cell Function and Antibodies Mediating ADCC in HIV-1-Infected Viremic and Controller Patients
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DOI：
10.1089/vim.2011.0025
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发表时间：
2011-10-01
期刊：
影响因子：
2.2
通讯作者：
Berg, Louise
中科院分区：
文献类型：
--
作者：
Johansson, Susanne E.;Rollman, Erik;Berg, Louise
自然杀伤（NK）细胞已被认为在HIV疾病进展中发挥保护作用。NK细胞的一种有效效应机制是抗体依赖性细胞毒性（ADCC），由NK细胞上与Fc γ RIIIa受体（CD16）结合的抗病毒抗体介导。我们研究了20名hiv -1感染患者和10名健康供者血浆中NK细胞介导的ADCC功能和ADCC抗体的存在。hiv阳性患者被分为两组：6人在不接受治疗的情况下控制了病毒血症至少8年（对照组），14人持续病毒血症且目前未接受治疗。两组患者血浆诱导NK细胞ifn - γ表达和脱颗粒反应HIV-1包膜（Env） gp140蛋白包被细胞。介导ADCC的患者抗体主要指向Env V3环，通过缺乏V3环的gp140蛋白鉴定。有趣的是，在两个控制者中，adc介导的抗体更广泛地指向Env的其他部分。患者的高病毒载量与adcc介导的gp140蛋白包被靶细胞的细胞溶解减少相关。来自感染患者和健康供体的NK细胞在抗体包被hiv -1感染的Jurkat细胞存在下都能有效地脱颗粒。总之，与病毒血症患者相比，一些控制者的adc介导抗体的特性有所不同。NK细胞ADCC活性在hiv感染患者中不受损害。
Natural killer (NK) cells have been suggested to play a protective role in HIV disease progression. One potent effector mechanism of NK cells is antibody-dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding to the Fc gamma RIIIa receptor (CD16) on NK cells. We investigated NK cell-mediated ADCC function and the presence of ADCC antibodies in plasma from 20 HIV-1-infected patients and 10 healthy donors. The HIV-positive patients were divided into two groups: six who controlled viremia for at least 8 y without treatment (controllers), and 14 who were persistently viremic and not currently on treatment. Plasma from both patient groups induced NK cell IFN-gamma expression and degranulation in response to HIV-1 envelope (Env) gp140-protein-coated cells. Patient antibodies mediating ADCC were largely directed towards the Env V3 loop, as identified by a gp140 protein lacking the V3 loop. Interestingly, in two controllers ADCC-mediating antibodies were more broadly directed to other parts of Env. A high viral load in patients correlated with decreased ADCC-mediated cytolysis of gp140-protein-coated target cells. NK cells from both infected patients and healthy donors degranulated efficiently in the presence of antibody-coated HIV-1-infected Jurkat cells. In conclusion, the character of ADCC-mediating antibodies differed in some controllers compared to viremic patients. NK cell ADCC activity is not compromised in HIV-infected patients.