Holl Vincent, Hemmerter Stéphane, Burrer Renaud, Schmidt Sylvie, Bohbot Alain, Aubertin Anne-Marie, Moog Christiane
Equipe d'Accueil 3770, Université Louis Pasteur (ULP), Institut de Virologie, 3 rue Koeberlé, 67000 Strasbourg, France.
J Immunol. 2004 Nov 15;173(10):6274-83. doi: 10.4049/jimmunol.173.10.6274.
The aim of this study was to investigate the mechanism of HIV-1 neutralization using monocyte-derived macrophages (MDM) in comparison to PBMC as target cells. For this purpose, we analyzed neutralizing activities of different human polyclonal IgG samples purified from sera of HIV-1-infected individuals using a single cycle infection assay. We found an increase of the neutralizing titer when macrophages vs PBMC were used as target cells. Moreover, polyclonal IgG from HIV-1-infected patients that are not able to neutralize virus when PBMC are used as target cells strongly inhibit MDM infection. Similar results were obtained with neutralizing mAbs. To explore the participation of FcgammaRs in HIV-1 inhibition, F(ab')(2) and Fab of these Igs were produced. Results indicated that both F(ab')(2) and Fab are less effective to inhibit virus replication in MDM. Moreover, competition experiments with Fc fragments of IgG from healthy donors or with purified monoclonal anti-human FcgammaRs Ab strengthen the participation of the FcgammaRs, and in particular of FcgammaRI (CD64) in HIV-1 inhibition on MDM. Mechanisms by which HIV-specific IgG inhibit virus replication in cultured macrophages are proposed and the benefit of inducing such Abs by vaccination is discussed.
本研究的目的是比较以单核细胞衍生的巨噬细胞（MDM）和外周血单个核细胞（PBMC）作为靶细胞时，HIV-1中和作用的机制。为此，我们使用单循环感染试验分析了从HIV-1感染个体血清中纯化的不同人多克隆IgG样本的中和活性。我们发现，当以巨噬细胞而非PBMC作为靶细胞时，中和效价有所增加。此外，当以PBMC作为靶细胞时无法中和病毒的HIV-1感染患者的多克隆IgG，能强烈抑制MDM感染。使用中和单克隆抗体也获得了类似结果。为了探究FcγR在HIV-1抑制中的作用，制备了这些Ig的F(ab')(2)和Fab片段。结果表明，F(ab')(2)和Fab在抑制MDM中的病毒复制方面效果较差。此外，与健康供体的IgG Fc片段或纯化的抗人FcγR单克隆抗体进行的竞争实验，进一步证实了FcγR，尤其是FcγRI（CD64）在MDM对HIV-1的抑制作用中的参与。本文提出了HIV特异性IgG抑制培养巨噬细胞中病毒复制的机制，并讨论了通过疫苗接种诱导此类抗体的益处。
