Rates of CTL killing in persistent viral infection in vivo.
Rates of CTL killing in persistent viral infection in vivo.
复制标题
体内持续病毒感染中CTL杀死的速率。
DOI：
10.1371/journal.pcbi.1003534
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发表时间：
2014-04
影响因子：
4.3
通讯作者：
Asquith B
中科院分区：
文献类型：
--
作者：
Elemans M;Florins A;Willems L;Asquith B
CD 8+细胞毒性T淋巴细胞（CTL）应答是抵抗病毒入侵的重要防御。尽管CTL介导的细胞毒性已被广泛研究多年，但对病毒感染的细胞在体内被CTL应答杀死的速率知之甚少。迄今为止，已经估计了三种病毒感染的体内CTL杀伤率，但估计值差异很大，并且对HIV-1感染细胞的杀伤出乎意料地低。这就提出了关于CTL的典型抗病毒能力以及CTL杀伤在HIV-1中是否异常低的问题。我们估计了两种不同的持续性病毒感染中CD 8 + T细胞对感染细胞的杀伤率：感染牛白血病病毒（BLV）的绵羊和感染人类嗜T细胞性病毒1型（HTLV-1）的人类，与现有数据一起，我们可以并行研究总共5种病毒。尽管BLV和HTLV-1感染的特征是慢性激活的CTL大量扩增，具有离体的直接效应子功能，并且没有明显的免疫抑制证据，但我们的估计值处于报告范围的低端。这使我们能够将目前的估计纳入视野，并表明CTL对HIV感染细胞的杀伤可能并不低。在范围的较高端处的估计是在更多操纵的系统中获得的，并且因此可以代表潜在的而不是实现的CTL效率。病毒复制受到一系列先天性和适应性宿主防御的反击。一种重要且广泛研究的适应性防御是CD 8+细胞毒性T淋巴细胞（CTL）应答。CTL的体内裂解能力的定量对于详细理解免疫应答是必不可少的。这包括理解病毒复制和病毒清除之间的平衡，理解CTL杀伤中的限速步骤，从而理解如何增加杀伤，以及理解CTL疫苗的失败。然而，人们对体内病毒感染细胞被CTL反应杀死的典型速率知之甚少。目前的估计数差异很大，对HIV-1感染的估计数特别低。我们估计了在两种不同的持续性病毒感染中CD 8 + T细胞对感染细胞的杀伤率，这使我们能够正确看待目前的估计。我们表明，CTL杀伤HIV感染的细胞可能不是致命的低。在范围的较高端处的估计是在更多操纵的系统中获得的，并且因此可以代表潜在的而不是实现的CTL效率。
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. Virus replication is countered by a range of innate and adaptive host defences. One important and widely studied adaptive defence is the CD8+ cytotoxic T lymphocyte (CTL) response. Quantification of the in vivo lytic capability of CTLs is essential for a detailed understanding of the immune response. This includes understanding the balance between viral replication and viral clearance, understanding the rate limiting steps in CTL killing and thus how killing can be increased and understanding the failure of CTL vaccines. However, the typical rate at which virus-infected cells are killed by the CTL response in vivo is poorly understood. Current estimates differ considerably and are especially low for HIV-1-infection. We estimated the rate of killing of infected cells by CD8+ T cells in two distinct persistent virus infections which enables us to put current estimates into perspective. We show 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.
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影响因子：
3.7
作者：
Ganusov VV;Lukacher AE;Byers AM
通讯作者：
Byers AM
影响因子：
5.4
作者：
Florins, Arnaud;de Brogniez, Alix;Willems, Luc
通讯作者：
Willems, Luc
影响因子：
5.4
作者：
Debacq, Christophe;Gillet, Nicolas;Willems, Luc
通讯作者：
Willems, Luc
影响因子：
9.8
作者：
Asquith B;Edwards CT;Lipsitch M;McLean AR
通讯作者：
McLean AR
DOI：
10.1073/pnas.0608832104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Asquith, Becca;Zhang, Yan;Bangham, Charles R. M.
通讯作者：
Bangham, Charles R. M.