Fu Tong-Ming, Dubey Sheri A, Mehrotra Devan V, Freed Daniel C, Trigona Wendy L, Adams-Muhler Lisa, Clair James H, Evans Thomas G, Steigbigel Roy, Jacobson Jeffrey M, Goepfert Paul A, Mulligan Mark J, Kalams Spyros A, Rinaldo Charles, Zhu Lan, Cox Kara S, Guan Liming, Long Romnie, Persaud Natasha, Caulfield Michael J, Sadoff Jerald C, Emini Emilio A, Thaler Scott, Shiver John W
Merck Research Laboratories, West Point, PA 19486, USA.
AIDS Res Hum Retroviruses. 2007 Jan;23(1):67-76. doi: 10.1089/aid.2006.0114.
The importance of host cellular immune responses, particularly CD8(+) cytotoxic T-lymphocyte (CTL) responses, in control of human immunodeficiency virus type 1 (HIV-1) infection has been demonstrated in many clinical studies. These studies, along with vaccination challenge studies in rhesus macaques, indicate the importance of cellular immune responses against HIV-1. Toward this end, we evaluated anti-HIV-1 cellular immune responses in a cohort of 54 subjects who were chronically infected with HIV-1. By validation of IFN-gamma ELISpot assay, we established a dual cut-off criterion for scoring a positive response. The magnitude and frequency of cellular immune responses were measured against HIV-1 antigens (Gag, Pol, Nef, Rev, and Tat), using synthetic peptides as antigens in ELISpot assay. Here we showed that HIV-1 Gag, Pol, and Nef were frequent targets of T cell responses in these subjects, whereas Tat and Rev were less frequently recognized. We further evaluated the possible association between host cellular immune responses and corresponding plasma viral loads in this cohort. By performing ranking correlation analysis, we demonstrated a positive correlation between host viral loads and ELISpot responses of HIV Gag and Pol in untreated subjects. For the subjects under antiviral regimens, however, we did not find any significant association. Our findings suggest that the high levels of ELISpot responses in chronically infected subjects were reflective of their persistent viral infection.
宿主细胞免疫反应,尤其是CD8(+)细胞毒性T淋巴细胞(CTL)反应,在控制人类免疫缺陷病毒1型(HIV-1)感染中的重要性已在许多临床研究中得到证实。这些研究以及恒河猴的疫苗接种挑战研究表明了针对HIV-1的细胞免疫反应的重要性。为此,我们评估了54名慢性感染HIV-1的受试者队列中的抗HIV-1细胞免疫反应。通过对干扰素-γ酶联免疫斑点试验(IFN-γ ELISpot试验)的验证,我们建立了用于对阳性反应进行评分的双重临界标准。在ELISpot试验中,使用合成肽作为抗原,针对HIV-1抗原(Gag、Pol、Nef、Rev和Tat)测量细胞免疫反应的强度和频率。在这里我们表明,HIV-1 Gag、Pol和Nef是这些受试者中T细胞反应的常见靶点,而Tat和Rev较少被识别。我们进一步评估了该队列中宿主细胞免疫反应与相应血浆病毒载量之间的可能关联。通过进行等级相关分析,我们证明了未治疗受试者中宿主病毒载量与HIV Gag和Pol的ELISpot反应之间存在正相关。然而,对于接受抗病毒治疗方案的受试者,我们未发现任何显著关联。我们的研究结果表明,慢性感染受试者中高水平的ELISpot反应反映了他们持续的病毒感染。