期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.03162
关键词
human immunodeficiency virus; HIV-1 reservoir; HIV-1 immunogen; shock and kill; CTL (Cytotoxic T lymphocyte); inhibitory receptors
类别
资金
- National Health Institute Carlos III (ISCIII) [PI14/01058, PI17/00168, PI14/01235, PI17/01470]
- Gilead [GLD 15/00298]
- Redes Tematicas de Investigacion en SIDA [ISCIII RETIC RD16/0025/0041]
- Accion Estrategica en Salud
- Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica
- Instituto de Salud Carlos III
- Fondos FEDER
- ISCIII [CPII15/00014]
- Catalan Government
- Spanish Ministry of Education, Culture and Sport [FPU15/03698]
The so-called shock and kill therapies aim to combine HIV-1 reactivation by latency-reversing agents (LRA) with immune clearance to purge the HIV-1 reservoir. The clinical use of LRA has demonstrated detectable perturbations in the HIV-1 reservoir without measurable reductions to date. Consequently, fundamental questions concerning the limitations of the recognition and killing of LRA-reactivated cells by effector cells such as CD8+ T cells remain to be answered. Here, we developed a novel experimental framework where we combine the use of cytotoxic CD8+ T-cell lines and ex vivo CD8+ T cells from HIV-1-infected individuals with functional assays of LRA-inducible reactivation to delineate immune barriers to clear the reservoir. Our results demonstrate the potential for early recognition and killing of reactivated cells by CD8+ T cells. However, the potency of LRAs when crossing the barrier for antigen presentation in target cells, together with the lack of expression of inhibitory receptors in CD8+ T cells, are critical events to maximize the speed of recognition and the magnitude of the killing of LRA-inducible provirus. Taken together, our findings highlight direct limitations in LRA potency and CD8+ T cell functional status to succeed in the cure of HIV-1 infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据