Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers
Cytolytic CD4+ T cells play a prominent role in chronic viral infection. CD4+ CTLs clones specific for HIV-1 Nef and Gag are capable of killing HIV-1 infected CD4+ T cells and macrophages. Additionally, HIV-specific cytolytic CD4+ T cell responses in acute HIV infection are predictive of disease pro...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01844/full |
| _version_ | 1828410431488655360 |
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| author | Chansavath Phetsouphanh Daniel Aldridge Emanuele Marchi C. Mee Ling Munier Jodi Meyerowitz Lyle Murray Cloete Van Vuuren Dominique Goedhals Sarah Fidler Anthony Kelleher Paul Klenerman John Frater |
| author_facet | Chansavath Phetsouphanh Daniel Aldridge Emanuele Marchi C. Mee Ling Munier Jodi Meyerowitz Lyle Murray Cloete Van Vuuren Dominique Goedhals Sarah Fidler Anthony Kelleher Paul Klenerman John Frater |
| author_sort | Chansavath Phetsouphanh |
| collection | DOAJ |
| description | Cytolytic CD4+ T cells play a prominent role in chronic viral infection. CD4+ CTLs clones specific for HIV-1 Nef and Gag are capable of killing HIV-1 infected CD4+ T cells and macrophages. Additionally, HIV-specific cytolytic CD4+ T cell responses in acute HIV infection are predictive of disease progression. CD57 expression on CD4s identifies cytolytic cells. These cells were dramatically increased in chronic HIV infection. CD57 expression correlated with cytolytic granules, granzyme B and perforin expression. They express lower CCR5 compared to CD57– cells, have less HIV total DNA, and were a minor component of the HIV reservoir. A small percentage of CD57+ CD4+ CTLs from EC were HIV-specific, could upregulate IFNγ with Gag peptide stimulation, express cytolytic granule markers and maintain TbethighEomes+ transcription factor phenotype. This was not observed in viraemic controllers. The maintenance of HIV-specific CD4 cytolytic function in Elite controllers together with CD8 CTLs may be important for the control of HIV viraemia and of potential relevance to cure strategies. |
| first_indexed | 2024-12-10T12:11:04Z |
| format | Article |
| id | doaj.art-bd0096d737aa4648b31a63218af7bdc9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T12:11:04Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bd0096d737aa4648b31a63218af7bdc92022-12-22T01:49:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.01844455888Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite ControllersChansavath Phetsouphanh0Daniel Aldridge1Emanuele Marchi2C. Mee Ling Munier3Jodi Meyerowitz4Lyle Murray5Cloete Van Vuuren6Dominique Goedhals7Sarah Fidler8Anthony Kelleher9Paul Klenerman10John Frater11Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomDepartment of Medicine, University of New South Wales, Sydney, NSW, AustraliaPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomMilitary Hospital, Bloemfontein, South AfricaNational Health Laboratory Service, Division of Virology, University of the Free State, Bloemfontein, South AfricaImperial College London, London, United KingdomDepartment of Medicine, University of New South Wales, Sydney, NSW, AustraliaPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United KingdomCytolytic CD4+ T cells play a prominent role in chronic viral infection. CD4+ CTLs clones specific for HIV-1 Nef and Gag are capable of killing HIV-1 infected CD4+ T cells and macrophages. Additionally, HIV-specific cytolytic CD4+ T cell responses in acute HIV infection are predictive of disease progression. CD57 expression on CD4s identifies cytolytic cells. These cells were dramatically increased in chronic HIV infection. CD57 expression correlated with cytolytic granules, granzyme B and perforin expression. They express lower CCR5 compared to CD57– cells, have less HIV total DNA, and were a minor component of the HIV reservoir. A small percentage of CD57+ CD4+ CTLs from EC were HIV-specific, could upregulate IFNγ with Gag peptide stimulation, express cytolytic granule markers and maintain TbethighEomes+ transcription factor phenotype. This was not observed in viraemic controllers. The maintenance of HIV-specific CD4 cytolytic function in Elite controllers together with CD8 CTLs may be important for the control of HIV viraemia and of potential relevance to cure strategies.https://www.frontiersin.org/article/10.3389/fimmu.2019.01844/fullT cellsHIVviral immunologyCD4 T cellscytotoxic T cells |
| spellingShingle | Chansavath Phetsouphanh Daniel Aldridge Emanuele Marchi C. Mee Ling Munier Jodi Meyerowitz Lyle Murray Cloete Van Vuuren Dominique Goedhals Sarah Fidler Anthony Kelleher Paul Klenerman John Frater Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers Frontiers in Immunology T cells HIV viral immunology CD4 T cells cytotoxic T cells |
| title | Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers |
| title_full | Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers |
| title_fullStr | Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers |
| title_full_unstemmed | Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers |
| title_short | Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers |
| title_sort | maintenance of functional cd57 cytolytic cd4 t cells in hiv elite controllers |
| topic | T cells HIV viral immunology CD4 T cells cytotoxic T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01844/full |
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