IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro

• Published in: Journal of immunology research Vol. 2019; no. 2019; pp. 1 - 13
• Main Authors: Huang, Zhaofeng, Tang, Xiao-ping, Xia, Jinyu, Li, Xuefeng, Zhang, Hui, Zhang, Yiwen, Li, Linghua, Pan, Ting, Liu, Bingfeng, Yu, Fei, Hong, Zhongsi, Li, Xinghua, Zhang, Xu, Zhang, Shaoying, Wu, Kang, Cai, Weiping
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2019; Hindawi; Hindawi Limited; Wiley
• Subjects: Antigens; Antiretroviral agents; Antiretroviral therapy; Blood & organ donations; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cohort Studies; Cytokines; Cytotoxicity; Drug therapy; Epitopes; Epitopes - immunology; HIV; HIV Antigens - immunology; HIV Infections - immunology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immune system; Immunologic Memory; Immunological memory; Immunology; Immunotherapy; Infections; Interferon-gamma - metabolism; Interleukin 15; Interleukin 21; Interleukin 9; Interleukin-15 - metabolism; Interleukins - metabolism; Latent infection; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Memory cells; Mutation; Patients; Peptides; Peripheral blood; Polymerase chain reaction; Replication; Ribonucleic acid; RNA; Stem cells; Viremia; Virus Replication; γ-Interferon; Japan
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2019/1801560

Due to the existence of viral reservoirs, the rebound of human immunodeficiency virus type 1 (HIV-1) viremia can occur within weeks after discontinuing combined antiretroviral therapy. Immunotherapy could potentially be applied to eradicate reactivated HIV-1 in latently infected CD4+ T lymphocytes. Although the existence of HIV-1-specific CD8+ T memory stem cells (TSCMs) is well established, there are currently no reports regarding methods using CD8+ TSCMs to treat HIV-1 infection. In this study, we quantified peripheral blood antigen-specific CD8+ TSCMs and then expanded HIV-1-specific TSCMs that targeted optimal antigen epitopes (SL9, IL9, and TL9) in the presence of interleukin- (IL-) 21 or IL-15. The suppressive capacity of the expanded CD8+ TSCMs on HIV-1 production was measured by assessing cell-associated viral RNA and performing viral outgrowth assays. We found that the number of unmutated TL9-specific CD8+ TSCMs positively correlated with the abundance of CD4+ T cells and that the expression of IFN-γ was higher in TL9-specific CD8+ TSCMs than that in non-TL9-specific CD8+ TSCMs. Moreover, the antiviral capacities of IL-21-stimulated CD8+ TSCMs exceeded those of conventional CD8+ memory T cells and IL-15-stimulated CD8+ TSCMs. Thus, we demonstrated that IL-21 could efficiently expand HIV-1-specific CD8+ TSCMs to suppress HIV-1 replication. Our study provides new insight into the function of IL-21 in the in vitro suppression of HIV-1 replication.