Hildreth J E, Hampton R, Halsey N A
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Clin Immunol. 1999 Feb;90(2):203-12. doi: 10.1006/clim.1998.4624.
We have developed a novel in vitro assay system to study the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in protection against HIV-1 infection by cell-associated virus. HIV-1-infected NK-resistant cells are mixed with specific antibody and unstimulated PBMC and ADCC is allowed to occur over several hours. The PBMC are then activated and cultured to allow virus replication in newly infected T cells. To ensure that ADCC is the only mechanism by which protection could occur we have used haptenated (TNP) infected cells and anti-hapten antibody. Anti-hapten sera completely protected PBMC from infection by haptenated HIV-1-infected cells in ADCC protection assays. F(ab')2 fragments of anti-hapten IgG showed no protection, confirming that ADCC was responsible for protection by anti-hapten IgG. PCR analysis for HIV-1 DNA confirmed the elimination of infected cells. We believe this to be the first direct demonstration that ADCC alone can protect PBMC from infection by cell-associated HIV-1.
我们开发了一种新型体外检测系统,以研究抗体依赖性细胞介导的细胞毒性(ADCC)在抵御细胞相关病毒引起的HIV-1感染中的作用。将感染HIV-1的NK抗性细胞与特异性抗体和未刺激的外周血单核细胞(PBMC)混合,让ADCC在数小时内发生。然后激活并培养PBMC,以使病毒在新感染的T细胞中复制。为确保ADCC是可能发生保护作用的唯一机制,我们使用了经半抗原化(TNP)的感染细胞和抗半抗原抗体。在ADCC保护试验中,抗半抗原血清完全保护PBMC免受经半抗原化的HIV-1感染细胞的感染。抗半抗原IgG的F(ab')2片段未显示出保护作用,证实ADCC是抗半抗原IgG发挥保护作用的原因。对HIV-1 DNA的PCR分析证实了感染细胞的清除。我们认为这是首次直接证明单独的ADCC可保护PBMC免受细胞相关HIV-1的感染。