Parsons Matthew S, Richard Jonathan, Lee Wen Shi, Vanderven Hillary, Grant Michael D, Finzi Andrés, Kent Stephen J
1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Australia .
2 Department of Microbiology, Infectiology and Immunology, Centre de Recherche du CHUM, Université de Montreal , Montreal, Canada .
AIDS Res Hum Retroviruses. 2016 Oct/Nov;32(10-11):1089-1096. doi: 10.1089/AID.2016.0099. Epub 2016 Sep 7.
The utility of antibody-dependent cellular cytotoxicity (ADCC) for eliminating HIV-1-infected cells is of much interest for the design of both prophylactic vaccines for HIV-1 prevention and therapeutics to eliminate latently infected cells following reactivation. Significant research has been conducted to understand the antibody specificities involved in anti-HIV-1 ADCC responses. Perhaps equally important as the identity of the antibodies mediating these responses are factors regulating the ability of ADCC effector cells, in particular, natural killer (NK) cells, to respond to antibody-coated target cells. Indeed, a plethora of activating and inhibitory receptors expressed on the surface of NK cells might act in conjunction with CD16 to influence ADCC. As the expression of NKG2D and its ligands has been linked to HIV-1 disease progression, we evaluated if signals through NKG2D were involved in anti-HIV-1 ADCC. Utilizing assays measuring cytolysis, we provide the first data implicating NKG2D in antibody-dependent NK cell responses against a target cell line either pulsed with gp120 or infected with HIV-1. These observations are highly significant for understanding antibody-dependent NK cell responses against HIV-1 and might be useful for optimizing prophylactics and therapeutics aiming to utilize antibodies and optimally functional NK cells to control HIV-1.
抗体依赖性细胞毒性（ADCC）在清除HIV-1感染细胞方面的效用，对于设计预防HIV-1的预防性疫苗以及重新激活后清除潜伏感染细胞的治疗方法而言，具有重要意义。为了了解抗HIV-1 ADCC反应中涉及的抗体特异性，已经开展了大量研究。或许与介导这些反应的抗体的特性同样重要的是调节ADCC效应细胞，特别是自然杀伤（NK）细胞对抗体包被靶细胞作出反应能力的因素。事实上，NK细胞表面表达的大量激活和抑制性受体可能与CD16协同作用，影响ADCC。由于NKG2D及其配体的表达与HIV-1疾病进展有关，我们评估了通过NKG2D传递的信号是否参与抗HIV-1 ADCC。利用测量细胞溶解的试验，我们首次提供了数据，表明NKG2D参与针对用gp120脉冲处理或感染HIV-1的靶细胞系的抗体依赖性NK细胞反应。这些观察结果对于理解针对HIV-1的抗体依赖性NK细胞反应具有重要意义，并且可能有助于优化旨在利用抗体和功能最佳的NK细胞来控制HIV-1的预防和治疗方法。
