Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
HIV Med. 2013 Apr;14(4):241-6. doi: 10.1111/j.1468-1293.2012.01040.x. Epub 2012 Aug 30.
Antiretroviral therapy (ART) suppresses HIV viraemia, thereby reducing the antigenic drive for T cells to proliferate. Accordingly, selected HIV-specific T-cell responses have been described to contract within weeks of ART initiation. Here, we sought to investigate whether these findings apply to the entire repertoire of HIV-specific T cells.
Using interferon (IFN)-γ enzyme linked immuno spot (ELISpot), we performed retrospective 2-year proteome-wide monitoring of HIV-specific T cells in 17 individuals with undetectable viral loads during ART. The sample pool for each study subject consisted of one pre-ART time-point and at least two time-points after initiation of therapy.
Peripheral pools of HIV-specific T cells decreased nonsignificantly within the first 2 years under ART in our cohort of patients, in terms of both breadth and magnitude. However, in most cases, the seeming decrease masked ongoing expansion of individual HIV-specific T-cell responses. We detected synchronous contraction and expansion of T-cell responses - with different peptide specificities - in 12 out of 17 study participants during follow-up. Importantly, the observed expansions and contractions of individual HIV-specific T-cell responses reached similar ranges, supporting the biological relevance of our findings.
We conclude that successful ART enables both contraction and expansion of HIV-specific T-cell responses. Our results should prompt a renewed interest in HIV-specific T-cell dynamics under ART, in particular to elucidate the mechanisms that uncouple, to some extent, particular HIV-specific T-cell responses from variations in circulating antigen load and functionally characterize expanding/contracting T-cell populations beyond IFN-γ secretion. Assuming that expanding HIV-specific T-cell responses under ART are protective and functional, harnessing those mechanisms may provide novel opportunities for assisting viral control in chronically infected individuals.
抗逆转录病毒疗法（ART）抑制 HIV 病毒血症，从而降低 T 细胞增殖的抗原驱动。因此，在 ART 开始后的数周内，已经描述了选择的 HIV 特异性 T 细胞反应会收缩。在这里，我们试图研究这些发现是否适用于 HIV 特异性 T 细胞的整个库。
使用干扰素（IFN）-γ酶联免疫斑点（ELISpot），我们对 17 名接受 ART 治疗且病毒载量不可检测的个体进行了为期 2 年的 HIV 特异性 T 细胞全蛋白质组回顾性监测。每个研究对象的样本池由一个 ART 前时间点和至少两个治疗开始后的时间点组成。
在我们的患者队列中，在 ART 的头 2 年内，HIV 特异性 T 细胞的外周池在广度和幅度上均无显著下降。然而，在大多数情况下，看似的下降掩盖了个别 HIV 特异性 T 细胞反应的持续扩张。我们在 17 名研究参与者中的 12 名参与者中检测到 T 细胞反应的同步收缩和扩张 - 具有不同的肽特异性 - 在随访期间。重要的是，观察到的个别 HIV 特异性 T 细胞反应的扩张和收缩达到了相似的范围，支持了我们研究结果的生物学相关性。
我们得出结论，成功的 ART 既能使 HIV 特异性 T 细胞反应收缩又能使其扩张。我们的研究结果应促使人们重新关注 ART 下 HIV 特异性 T 细胞的动态变化，特别是阐明在一定程度上使特定的 HIV 特异性 T 细胞反应与循环抗原负荷的变化解耦的机制，并超越 IFN-γ 分泌功能特征化扩张/收缩的 T 细胞群体。假设在 ART 下扩增的 HIV 特异性 T 细胞反应具有保护性和功能性，利用这些机制可能为慢性感染个体的病毒控制提供新的机会。
