Elemans Marjet, Florins Arnaud, Willems Luc, Asquith Becca
Section of Immunology, Imperial College London, London, United Kingdom.
Molecular and Cellular Biology, Université de Liège and GIGA, Gembloux Agro-Bio Tech, Liège, Belgium.
PLoS Comput Biol. 2014 Apr 3;10(4):e1003534. doi: 10.1371/journal.pcbi.1003534. eCollection 2014 Apr.
The CD8+ cytotoxic T lymphocyte (CTL) response is an important defence against viral invasion. Although CTL-mediated cytotoxicity has been widely studied for many years, the rate at which virus-infected cells are killed in vivo by the CTL response is poorly understood. To date the rate of CTL killing in vivo has been estimated for three virus infections but the estimates differ considerably, and killing of HIV-1-infected cells was unexpectedly low. This raises questions about the typical anti-viral capability of CTL and whether CTL killing is abnormally low in HIV-1. We estimated the rate of killing of infected cells by CD8+ T cells in two distinct persistent virus infections: sheep infected with Bovine Leukemia Virus (BLV) and humans infected with Human T Lymphotropic Virus type 1 (HTLV-1) which together with existing data allows us to study a total of five viruses in parallel. Although both BLV and HTLV-1 infection are characterised by large expansions of chronically activated CTL with immediate effector function ex vivo and no evidence of overt immune suppression, our estimates are at the lower end of the reported range. This enables us to put current estimates into perspective and shows that CTL killing of HIV-infected cells may not be atypically low. The estimates at the higher end of the range are obtained in more manipulated systems and may thus represent the potential rather than the realised CTL efficiency.
CD8 + 细胞毒性T淋巴细胞（CTL）反应是抵御病毒入侵的重要防御机制。尽管CTL介导的细胞毒性已被广泛研究多年，但CTL反应在体内杀死病毒感染细胞的速率仍知之甚少。迄今为止，已对三种病毒感染的体内CTL杀伤速率进行了估计，但这些估计差异很大，而且HIV-1感染细胞的杀伤率出人意料地低。这引发了关于CTL典型抗病毒能力以及HIV-1中CTL杀伤是否异常低的问题。我们估计了CD8 + T细胞在两种不同的持续性病毒感染中杀死感染细胞的速率：感染牛白血病病毒（BLV）的绵羊和感染1型人类嗜T淋巴细胞病毒（HTLV-1）的人类，结合现有数据，我们能够同时研究总共五种病毒。尽管BLV和HTLV-1感染的特征都是慢性活化的CTL大量扩增，体外具有即时效应功能，且没有明显免疫抑制的证据，但我们的估计处于报告范围的下限。这使我们能够正确看待当前的估计，并表明CTL对HIV感染细胞的杀伤可能并非异常低。范围上限的估计是在更多人工操作的系统中获得的，因此可能代表的是潜在而非实际的CTL效率。
