DataSheet_2_CCL5-Secreting Virtual Memory CD8+ T Cells Inversely Associate With Viral Reservoir Size in HIV‐1−Infected Individuals on Antiretroviral T.csv (31.73 kB)
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DataSheet_2_CCL5-Secreting Virtual Memory CD8+ T Cells Inversely Associate With Viral Reservoir Size in HIV‐1−Infected Individuals on Antiretroviral Therapy.csv

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posted on 03.06.2022, 09:19 authored by Wei Hu, Yan-Jun Li, Cheng Zhen, You-Yuan Wang, Hui-Huang Huang, Jun Zou, Yan-Qing Zheng, Gui-Chan Huang, Si-Run Meng, Jie-Hua Jin, Jing Li, Ming-Ju Zhou, Yu-Long Fu, Peng Zhang, Xiao-Yu Li, Tao Yang, Xiu-Wen Wang, Xiu-Han Yang, Jin-Wen Song, Xing Fan, Yan-Mei Jiao, Ruo-Nan Xu, Ji-Yuan Zhang, Chun-Bao Zhou, Jin-Hong Yuan, Lei Huang, Ya-Qin Qin, Feng-Yao Wu, Ming Shi, Fu-Sheng Wang, Chao Zhang

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.

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