PMID- 34987521 OWN - NLM STAT- MEDLINE DCOM- 20220225 LR - 20220225 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Increased Platelet-CD4(+) T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4(+) T Cell Loss. PG - 799124 LID - 10.3389/fimmu.2021.799124 [doi] LID - 799124 AB - Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4(+) T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4(+) T cell aggregates in the peripheral blood of treatment-naive HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4 (+) T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4 (+) T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4 (+) T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4 (+) T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4 (+) T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4(+) T cell aggregates imply the potential role in CD4(+) T cell loss during HIV-1 infection. Furthermore, platelet-CD4 (+) T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4 (+) T cell counterparts. The platelet-CD4 (+) T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4 (+) T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection. CI - Copyright (c) 2021 Dai, Wu, Cui, Liao, Jiao, Zhang, Song, Fan, Zhang, He and Wang. FAU - Dai, Xiao-Peng AU - Dai XP AD - Medical School of Chinese People's Liberation Army of China (PLA), Beijing, China. AD - Noncommissioned Officer School, Army Medical University, Shijiazhuang, China. FAU - Wu, Feng-Ying AU - Wu FY AD - Medical School of Chinese People's Liberation Army of China (PLA), Beijing, China. AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Cui, Cheng AU - Cui C AD - Noncommissioned Officer School, Army Medical University, Shijiazhuang, China. FAU - Liao, Xue-Jiao AU - Liao XJ AD - The Third People's Hospital of Shenzhen, School of Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Jiao, Yan-Mei AU - Jiao YM AD - Department of Infectious Diseases, The Fifth Medical Centre of Chinese People's Liberation Army of China (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. FAU - Zhang, Chao AU - Zhang C AD - Department of Infectious Diseases, The Fifth Medical Centre of Chinese People's Liberation Army of China (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. FAU - Song, Jin-Wen AU - Song JW AD - Department of Infectious Diseases, The Fifth Medical Centre of Chinese People's Liberation Army of China (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. FAU - Fan, Xing AU - Fan X AD - Department of Infectious Diseases, The Fifth Medical Centre of Chinese People's Liberation Army of China (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. FAU - Zhang, Ji-Yuan AU - Zhang JY AD - Department of Infectious Diseases, The Fifth Medical Centre of Chinese People's Liberation Army of China (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. FAU - He, Qing AU - He Q AD - The Third People's Hospital of Shenzhen, School of Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Wang, Fu-Sheng AU - Wang FS AD - Medical School of Chinese People's Liberation Army of China (PLA), Beijing, China. AD - Department of Infectious Diseases, The Fifth Medical Centre of Chinese People's Liberation Army of China (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211220 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Anti-Retroviral Agents) RN - 0 (Antigens, Viral) RN - 0 (Biomarkers, Pharmacological) RN - 0 (Gene Products, gag) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Adult MH - Anti-Retroviral Agents/therapeutic use MH - Antigens, Viral/immunology MH - Biomarkers, Pharmacological MH - Blood Platelets/*immunology MH - CD4 Lymphocyte Count MH - CD4-CD8 Ratio MH - CD4-Positive T-Lymphocytes/*immunology MH - Caspase 1/metabolism MH - Cell Adhesion MH - Cells, Cultured MH - Female MH - Gene Products, gag/immunology MH - HIV Infections/drug therapy/*immunology MH - HIV-1/*physiology MH - Humans MH - Inflammation/*immunology MH - Male MH - Middle Aged MH - Platelet Aggregation MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Viral Load MH - Young Adult PMC - PMC8720770 OTO - NOTNLM OT - HIV-1 OT - T cell loss OT - infection OT - permissiveness OT - platelet-CD4+ T cell aggregates COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/07 06:00 MHDA- 2022/02/26 06:00 PMCR- 2021/01/01 CRDT- 2022/01/06 05:53 PHST- 2021/10/21 00:00 [received] PHST- 2021/12/06 00:00 [accepted] PHST- 2022/01/06 05:53 [entrez] PHST- 2022/01/07 06:00 [pubmed] PHST- 2022/02/26 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.799124 [doi] PST - epublish SO - Front Immunol. 2021 Dec 20;12:799124. doi: 10.3389/fimmu.2021.799124. eCollection 2021.