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CTLA-4和PD-1记忆性CD4 T细胞在接受抗逆转录病毒治疗但SIV感染的恒河猴体内对病毒持续存在起关键作用。

CTLA-4PD-1 Memory CD4 T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques.

作者信息

McGary Colleen S, Deleage Claire, Harper Justin, Micci Luca, Ribeiro Susan P, Paganini Sara, Kuri-Cervantes Leticia, Benne Clarisse, Ryan Emily S, Balderas Robert, Jean Sherrie, Easley Kirk, Marconi Vincent, Silvestri Guido, Estes Jacob D, Sekaly Rafick-Pierre, Paiardini Mirko

机构信息

Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.

AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA.

出版信息

Immunity. 2017 Oct 17;47(4):776-788.e5. doi: 10.1016/j.immuni.2017.09.018.

DOI:10.1016/j.immuni.2017.09.018
PMID:29045906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5679306/
Abstract

Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1 follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4PD-1 memory CD4 T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1 Tfh cells, SIV-enriched CTLA-4PD-1 CD4 T cells were found outside the B cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4PD-1 memory CD4 T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure.

摘要

抗逆转录病毒疗法（ART）可抑制HIV感染者体内的病毒复制，但无法清除潜伏感染细胞库。近期研究发现，程序性死亡受体1滤泡辅助性T细胞（PD-1 Tfh细胞）是病毒持续存在的重要细胞区室。在此，我们利用接受ART治疗的感染猴免疫缺陷病毒（SIV）的恒河猴进行研究，结果显示，细胞毒性T淋巴细胞相关抗原4程序性死亡受体1记忆性CD4 T细胞（CTLA-4PD-1记忆性CD4 T细胞）与调节性T细胞具有共同的表型标志物，在血液、淋巴结（LN）、脾脏和肠道的SIV DNA中富集，且含有具有复制能力和传染性的病毒。与PD-1 Tfh细胞不同，富含SIV的CTLA-4PD-1 CD4 T细胞存在于LN的B细胞滤泡之外，可预测ART期间持续性病毒库的大小，并且随着ART介导的病毒抑制时间延长，其对SIV库的贡献显著增加。我们已经证明，CTLA-4PD-1记忆性CD4 T细胞是SIV和HIV病毒库中一个此前未被认识的组成部分，并应作为功能性治愈HIV-1的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/db16079b8292/nihms909903f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/509ae3328316/nihms909903f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/df9860792f15/nihms909903f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/db16079b8292/nihms909903f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/1e0f24c5a275/nihms909903f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/f79f96076267/nihms909903f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/2b9488995532/nihms909903f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/29594ef80725/nihms909903f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/509ae3328316/nihms909903f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/df9860792f15/nihms909903f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5d/5679306/db16079b8292/nihms909903f7.jpg

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