Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, London SW10 9NH, United Kingdom.
J Infect Dis. 2010 Mar;201(5):720-9. doi: 10.1086/650492.
We have characterized an assay measuring CD8 T cell-mediated inhibition of human immunodeficiency virus (HIV) type 1 replication, demonstrating specificity and reproducibility and employing a panel of primary HIV-1 isolates. The assay uses relatively simple autologous cell culture and enzyme-linked immunosorbent assay, avoids generation of T cell clones, and can be performed with <2 million peripheral blood mononuclear cells. Efficient CD8 T cell-mediated cross-clade inhibition of HIV-1 replication in vitro was demonstrated in antiretroviral therapy-naive HIV-1-infected subjects with controlled viral replication in vivo but not in viremic subjects. An HIV-1 vaccine candidate, consisting of DNA and recombinant adenovirus 5 vectors tested in a phase I clinical trial, induced CD8 T cells that efficiently inhibited HIV-1 in a HLA-I-dependent manner. Assessment of direct antiviral T cell function by this assay provides additional information to guide vaccine design and the prioritizing of candidates for further clinical trials.
我们描述了一种检测 CD8 T 细胞介导的抑制人类免疫缺陷病毒（HIV）1 型复制的方法，该方法具有特异性和重现性，并使用了一组原发性 HIV-1 分离物。该检测方法采用相对简单的自体细胞培养和酶联免疫吸附试验，避免了 T 细胞克隆的产生，并且可以使用少于 200 万个外周血单核细胞进行检测。在体内病毒复制得到控制但未处于病毒血症的抗逆转录病毒治疗初治 HIV-1 感染患者中，我们证明了 CD8 T 细胞能够有效地抑制 HIV-1 的跨群抑制。一种 HIV-1 疫苗候选物，由 DNA 和重组腺病毒 5 载体组成，在 I 期临床试验中进行了测试，诱导了以 HLA-I 依赖性方式有效抑制 HIV-1 的 CD8 T 细胞。通过该检测方法评估直接抗病毒 T 细胞功能，可提供更多信息，以指导疫苗设计，并优先选择候选疫苗进行进一步的临床试验。
