IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro
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....
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/1801560 |
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| author | Kang Wu Shaoying Zhang Xu Zhang Xinghua Li Zhongsi Hong Fei Yu Bingfeng Liu Ting Pan Zhaofeng Huang Xiao-ping Tang Weiping Cai Jinyu Xia Xuefeng Li Hui Zhang Yiwen Zhang Linghua Li |
| author_facet | Kang Wu Shaoying Zhang Xu Zhang Xinghua Li Zhongsi Hong Fei Yu Bingfeng Liu Ting Pan Zhaofeng Huang Xiao-ping Tang Weiping Cai Jinyu Xia Xuefeng Li Hui Zhang Yiwen Zhang Linghua Li |
| author_sort | Kang Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-66acd360ae7f483a9e4d1e7ef8b7106b |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-66acd360ae7f483a9e4d1e7ef8b7106b2025-08-20T02:23:41ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/18015601801560IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In VitroKang Wu0Shaoying Zhang1Xu Zhang2Xinghua Li3Zhongsi Hong4Fei Yu5Bingfeng Liu6Ting Pan7Zhaofeng Huang8Xiao-ping Tang9Weiping Cai10Jinyu Xia11Xuefeng Li12Hui Zhang13Yiwen Zhang14Linghua Li15Institute of Human Virology, ChinaNational-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, 710004, ChinaInstitute of Human Virology, ChinaDepartment of Infectious Diseases, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, ChinaDepartment of Infectious Diseases, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, ChinaInstitute of Human Virology, ChinaInstitute of Human Virology, ChinaInstitute of Human Virology, ChinaInstitute of Human Virology, ChinaDepartment of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, ChinaDepartment of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, ChinaDepartment of Infectious Diseases, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, ChinaInstitute of Human Virology, ChinaInstitute of Human Virology, ChinaInstitute of Human Virology, ChinaDepartment of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, ChinaDue 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.http://dx.doi.org/10.1155/2019/1801560 |
| spellingShingle | Kang Wu Shaoying Zhang Xu Zhang Xinghua Li Zhongsi Hong Fei Yu Bingfeng Liu Ting Pan Zhaofeng Huang Xiao-ping Tang Weiping Cai Jinyu Xia Xuefeng Li Hui Zhang Yiwen Zhang Linghua Li IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro Journal of Immunology Research |
| title | IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro |
| title_full | IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro |
| title_fullStr | IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro |
| title_full_unstemmed | IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro |
| title_short | IL-21 Expands HIV-1-Specific CD8+ T Memory Stem Cells to Suppress HIV-1 Replication In Vitro |
| title_sort | il 21 expands hiv 1 specific cd8 t memory stem cells to suppress hiv 1 replication in vitro |
| url | http://dx.doi.org/10.1155/2019/1801560 |
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