Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom ; HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2013 Sep 10;8(9):e74858. doi: 10.1371/journal.pone.0074858. eCollection 2013.
HIV-1 infected cells are eliminated in infected individuals by a variety of cellular mechanisms, the best characterized of which are cytotoxic T cell and NK cell-mediated killing. An additional antiviral mechanism is antibody-dependent cellular cytotoxicity. Here we use primary CD4(+) T cells infected with the BaL clone of HIV-1 as target cells and autologous NK cells, monocytes, and neutrophils as effector cells, to quantify the cytotoxicity mediated by the different effectors. This was carried out in the presence or absence of HIV-1-specific antiserum to assess antibody-dependent cellular cytotoxicity. We show that at the same effector to target ratio, NK cells and monocytes mediate similar levels of both antibody-dependent and antibody-independent killing of HIV-1-infected T cells. Neutrophils mediated significant antibody-dependent killing of targets, but were less effective than monocytes or NK cells. These data have implications for acquisition and control of HIV-1 in natural infection and in the context of vaccination.
在受感染的个体中,HIV-1 感染的细胞被多种细胞机制消除,其中最具特征的是细胞毒性 T 细胞和自然杀伤 (NK) 细胞介导的杀伤。另一种抗病毒机制是抗体依赖性细胞毒性。在这里,我们使用感染了 HIV-1BaL 克隆的原代 CD4(+)T 细胞作为靶细胞,以及自体 NK 细胞、单核细胞和中性粒细胞作为效应细胞,定量分析不同效应细胞介导的细胞毒性。这是在存在或不存在 HIV-1 特异性抗血清的情况下进行的,以评估抗体依赖性细胞毒性。我们表明,在相同的效应物与靶细胞比例下,NK 细胞和单核细胞介导 HIV-1 感染 T 细胞的抗体依赖性和非抗体依赖性杀伤水平相似。中性粒细胞介导了针对靶细胞的显著抗体依赖性杀伤,但不如单核细胞或 NK 细胞有效。这些数据对于自然感染和疫苗接种背景下 HIV-1 的获得和控制具有重要意义。