Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context
Background: HIV-1-specific CD8+ T cells are required for immune suppression of HIV-1 replication and elimination of the associated viral reservoirs. However, effective induction of functional HIV-1-specific CD8+ T cells from naïve cells remains problematic in the setting of human vaccine trials. In...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-04-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419302233 |
| _version_ | 1818173998509326336 |
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| author | Nozomi Kuse Xiaoming Sun Tomohiro Akahoshi Anna Lissina Takuya Yamamoto Victor Appay Masafumi Takiguchi |
| author_facet | Nozomi Kuse Xiaoming Sun Tomohiro Akahoshi Anna Lissina Takuya Yamamoto Victor Appay Masafumi Takiguchi |
| author_sort | Nozomi Kuse |
| collection | DOAJ |
| description | Background: HIV-1-specific CD8+ T cells are required for immune suppression of HIV-1 replication and elimination of the associated viral reservoirs. However, effective induction of functional HIV-1-specific CD8+ T cells from naïve cells remains problematic in the setting of human vaccine trials. In this study, we investigated priming of functional HIV-1-specific CD8+ T cells from naïve cells. Methods: HIV-1-specific CD8+ T cells were primed from naïve T cells of HIV-1-seronegative individuals using TLR4 ligand LPS or STING ligand 3′3′-cGAMP in vitro. We established HIV-1-specific CD8+ T cell lines from primed T cells and then investigated functional properties of these cells. Findings: HIV-1-specific CD8+ T cells primed with LPS failed to suppress HIV-1. In contrast, 3′3′-cGAMP effectively primed HIV-1-specific CD8+ T cells with strong ability to suppress HIV-1. 3′3′-cGAMP-primed T cells had higher expression levels of perforin and granzyme B than LPS-primed ones. The expression levels of granzyme B and perforin and viral suppression ability of 3′3′-cGAMP-primed T cells were positively correlated with the production level of type I IFN from PBMCs stimulated with 3′3′-cGAMP. Interpretation: The present study demonstrates the potential of 3′3′-cGAMP to induce HIV-1-specific CD8+ T cells with strong effector function from naïve cells via a strong type I IFN production and suggests that this STING ligand may be useful for AIDS vaccine and cure treatment. Keywords: HIV-1, CD8+ T cells, Priming, STING ligand, Naïve T cell |
| first_indexed | 2024-12-11T19:37:25Z |
| format | Article |
| id | doaj.art-8105d94cc3b1441b8a18911fe847a0e3 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T19:37:25Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-8105d94cc3b1441b8a18911fe847a0e32022-12-22T00:53:06ZengElsevierEBioMedicine2352-39642019-04-0142109119Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in contextNozomi Kuse0Xiaoming Sun1Tomohiro Akahoshi2Anna Lissina3Takuya Yamamoto4Victor Appay5Masafumi Takiguchi6Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, JapanCenter for AIDS Research, Kumamoto University, Kumamoto 860-0811, JapanCenter for AIDS Research, Kumamoto University, Kumamoto 860-0811, JapanSorbonne Universite, INSERM, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), F-75013 Paris, FranceLaboratory of Immunosenescence, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, JapanSorbonne Universite, INSERM, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), F-75013 Paris, France; International Research Center of Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, JapanCenter for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; Corresponding author at: Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.Background: HIV-1-specific CD8+ T cells are required for immune suppression of HIV-1 replication and elimination of the associated viral reservoirs. However, effective induction of functional HIV-1-specific CD8+ T cells from naïve cells remains problematic in the setting of human vaccine trials. In this study, we investigated priming of functional HIV-1-specific CD8+ T cells from naïve cells. Methods: HIV-1-specific CD8+ T cells were primed from naïve T cells of HIV-1-seronegative individuals using TLR4 ligand LPS or STING ligand 3′3′-cGAMP in vitro. We established HIV-1-specific CD8+ T cell lines from primed T cells and then investigated functional properties of these cells. Findings: HIV-1-specific CD8+ T cells primed with LPS failed to suppress HIV-1. In contrast, 3′3′-cGAMP effectively primed HIV-1-specific CD8+ T cells with strong ability to suppress HIV-1. 3′3′-cGAMP-primed T cells had higher expression levels of perforin and granzyme B than LPS-primed ones. The expression levels of granzyme B and perforin and viral suppression ability of 3′3′-cGAMP-primed T cells were positively correlated with the production level of type I IFN from PBMCs stimulated with 3′3′-cGAMP. Interpretation: The present study demonstrates the potential of 3′3′-cGAMP to induce HIV-1-specific CD8+ T cells with strong effector function from naïve cells via a strong type I IFN production and suggests that this STING ligand may be useful for AIDS vaccine and cure treatment. Keywords: HIV-1, CD8+ T cells, Priming, STING ligand, Naïve T cellhttp://www.sciencedirect.com/science/article/pii/S2352396419302233 |
| spellingShingle | Nozomi Kuse Xiaoming Sun Tomohiro Akahoshi Anna Lissina Takuya Yamamoto Victor Appay Masafumi Takiguchi Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context EBioMedicine |
| title | Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context |
| title_full | Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context |
| title_fullStr | Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context |
| title_full_unstemmed | Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context |
| title_short | Priming of HIV-1-specific CD8+ T cells with strong functional properties from naïve T cellsResearch in context |
| title_sort | priming of hiv 1 specific cd8 t cells with strong functional properties from naive t cellsresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419302233 |
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