Author:
Hu Wei,Li Yan-Jun,Zhen Cheng,Wang You-Yuan,Huang Hui-Huang,Zou Jun,Zheng Yan-Qing,Huang Gui-Chan,Meng Si-Run,Jin Jie-Hua,Li Jing,Zhou Ming-Ju,Fu Yu-Long,Zhang Peng,Li Xiao-Yu,Yang Tao,Wang Xiu-Wen,Yang Xiu-Han,Song Jin-Wen,Fan Xing,Jiao Yan-Mei,Xu Ruo-Nan,Zhang Ji-Yuan,Zhou Chun-Bao,Yuan Jin-Hong,Huang Lei,Qin Ya-Qin,Wu Feng-Yao,Shi Ming,Wang Fu-Sheng,Zhang Chao
Abstract
Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (TCM) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (TEMRA). Moreover, a virtual memory CD8+ T cell (TVM) subset was enriched in CCL4-CCL5+ TEMRA cells and phenotypically distinctive from CCL4+ TCM subset, supported by single-cell RNA-Seq data. Specifically, TVM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ TCM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, TVM cells inhibited HIV-1 reactivation more effectively than non-TVM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting TVM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease.
Funder
National Natural Science Foundation of China
National Science and Technology Major Project
Natural Science Foundation of Beijing Municipality
Subject
Immunology,Immunology and Allergy
Cited by
7 articles.
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