HIV 控制器对 HIV-1 感染的非激活 CD4 T 细胞表现出有效的 CD8 T 细胞识别。
HIV Controllers Exhibit Effective CD8 T Cell Recognition of HIV-1-Infected Non-activated CD4 T Cells.
机构信息
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
出版信息
Cell Rep. 2019 Apr 2;27(1):142-153.e4. doi: 10.1016/j.celrep.2019.03.016.
Even with sustained antiretroviral therapy, resting CD4 T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8 T cells recognize infected, non-activated CD4 T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8 T cells from HIV controllers mediate more effective immune recognition than CD8 T cells from progressors. These results indicate that non-activated HIV-infected CD4 T cells can be targeted by CD8 T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir.
即使持续进行抗逆转录病毒治疗，静止的 CD4 T 细胞仍然是 HIV 感染的持续储存库，这是治愈 HIV 的一个关键障碍。在这里，我们证明 CD8 T 细胞在没有新蛋白质产生的情况下识别感染的非激活的 CD4 T 细胞，如免疫突触形成、脱颗粒、细胞因子产生和杀伤感染细胞来衡量。免疫识别是由 HLA-I 呈递来自传入病毒颗粒的肽诱导的，并且识别发生在游离病毒感染后或细胞间传播后。来自 HIV 控制器的 CD8 T 细胞比进展者的 CD8 T 细胞介导更有效的免疫识别。这些结果表明，非激活的 HIV 感染的 CD4 T 细胞可以在 HIV 进入后、逆转录之前直接被 CD8 T 细胞靶向，因此在潜伏期建立之前，并且提示免疫反应可能减少 HIV 储存库的大小的机制。
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