Frontiers in Immunology (May 2022)
CCL5-Secreting Virtual Memory CD8+ T Cells Inversely Associate With Viral Reservoir Size in HIV‐1−Infected Individuals on Antiretroviral Therapy
- Wei Hu,
- Wei Hu,
- Yan-Jun Li,
- Cheng Zhen,
- You-Yuan Wang,
- 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,
- Fu-Sheng Wang,
- Fu-Sheng Wang,
- Chao Zhang,
- Chao Zhang
Affiliations
- Wei Hu
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, China
- Wei Hu
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Yan-Jun Li
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Cheng Zhen
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- You-Yuan Wang
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, China
- You-Yuan Wang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Hui-Huang Huang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Jun Zou
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Yan-Qing Zheng
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Gui-Chan Huang
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Si-Run Meng
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Jie-Hua Jin
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Jing Li
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Ming-Ju Zhou
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Yu-Long Fu
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Peng Zhang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Xiao-Yu Li
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Tao Yang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Xiu-Wen Wang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Xiu-Han Yang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Jin-Wen Song
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Xing Fan
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Yan-Mei Jiao
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Ruo-Nan Xu
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Ji-Yuan Zhang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Chun-Bao Zhou
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Jin-Hong Yuan
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Lei Huang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Ya-Qin Qin
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Feng-Yao Wu
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Ming Shi
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Fu-Sheng Wang
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, China
- Fu-Sheng Wang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Fu-Sheng Wang
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- Chao Zhang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Chao Zhang
- Guangxi Acquired Immune Deficiency Syndrome (AIDS) Clinical Treatment Centre, The Fourth People’s Hospital of Nanning, Nanning, China
- DOI
- https://doi.org/10.3389/fimmu.2022.897569
- Journal volume & issue
-
Vol. 13
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.
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