Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy
T cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.647688/full |
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| author | Genevieve E. Martin Genevieve E. Martin Debattama R. Sen Debattama R. Sen Matthew Pace Nicola Robinson Jodi Meyerowitz Emily Adland John P. Thornhill John P. Thornhill Mathew Jones Ane Ogbe Lucia Parolini Natalia Olejniczak Panagiota Zacharopoulou Helen Brown Christian B. Willberg Christian B. Willberg Nneka Nwokolo Julie Fox Julie Fox Sarah Fidler Sarah Fidler W. Nicholas Haining W. Nicholas Haining John Frater John Frater |
| author_facet | Genevieve E. Martin Genevieve E. Martin Debattama R. Sen Debattama R. Sen Matthew Pace Nicola Robinson Jodi Meyerowitz Emily Adland John P. Thornhill John P. Thornhill Mathew Jones Ane Ogbe Lucia Parolini Natalia Olejniczak Panagiota Zacharopoulou Helen Brown Christian B. Willberg Christian B. Willberg Nneka Nwokolo Julie Fox Julie Fox Sarah Fidler Sarah Fidler W. Nicholas Haining W. Nicholas Haining John Frater John Frater |
| author_sort | Genevieve E. Martin |
| collection | DOAJ |
| description | T cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated from early PHI with up to three years of ART. Compared with HIV-uninfected controls, CD4 and CD8 T cells from early HIV infection were characterised by T cell activation and increased expression of the immune checkpoint receptors (ICRs) PD1, Tim-3 and TIGIT. Three years of ART lead to partial – but not complete – normalisation of ICR expression, the dynamics of which varied for individual ICRs. For HIV-specific cells, epigenetic profiling of tetramer-sorted CD8 T cells revealed that epigenetic features of exhaustion typically seen in chronic HIV infection were already present early in PHI, and that ART initiation during PHI resulted in only a partial shift of the epigenome to one with more favourable memory characteristics. These findings suggest that although ART initiation during PHI results in significant immune reconstitution, there may be only partial resolution of HIV-related phenotypic and epigenetic changes. |
| first_indexed | 2024-12-21T15:41:30Z |
| format | Article |
| id | doaj.art-3d165a2ffd8b4a029910eb0c288ef7ef |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T15:41:30Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d165a2ffd8b4a029910eb0c288ef7ef2022-12-21T18:58:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.647688647688Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral TherapyGenevieve E. Martin0Genevieve E. Martin1Debattama R. Sen2Debattama R. Sen3Matthew Pace4Nicola Robinson5Jodi Meyerowitz6Emily Adland7John P. Thornhill8John P. Thornhill9Mathew Jones10Ane Ogbe11Lucia Parolini12Natalia Olejniczak13Panagiota Zacharopoulou14Helen Brown15Christian B. Willberg16Christian B. Willberg17Nneka Nwokolo18Julie Fox19Julie Fox20Sarah Fidler21Sarah Fidler22W. Nicholas Haining23W. Nicholas Haining24John Frater25John Frater26Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Infectious Diseases, Monash University, Melbourne, VIC, AustraliaDepartment of Immunology, Harvard Medical School, Boston, MA, United StatesDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United StatesPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Paediatrics, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomDivision of Medicine, Wright Fleming Institute, Imperial College, London, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomOxford National Institute of Health Research Biomedical Research Centre, Oxford, United KingdomChelsea and Westminster Hospital, London, United KingdomDepartment of Genitourinary Medicine and Infectious Disease, Guys and St Thomas’ National Health Service (NHS) Trust, London, United Kingdom0King’s College National Institute of Health Research (NIHR) Biomedical Research Centre, London, United KingdomDivision of Medicine, Wright Fleming Institute, Imperial College, London, United Kingdom1Imperial College NIHR Biomedical Research Centre, London, United KingdomDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States2Discovery Oncology and Immunology, Merck Research Laboratories, Boston, MA, United StatesPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomOxford National Institute of Health Research Biomedical Research Centre, Oxford, United KingdomT cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated from early PHI with up to three years of ART. Compared with HIV-uninfected controls, CD4 and CD8 T cells from early HIV infection were characterised by T cell activation and increased expression of the immune checkpoint receptors (ICRs) PD1, Tim-3 and TIGIT. Three years of ART lead to partial – but not complete – normalisation of ICR expression, the dynamics of which varied for individual ICRs. For HIV-specific cells, epigenetic profiling of tetramer-sorted CD8 T cells revealed that epigenetic features of exhaustion typically seen in chronic HIV infection were already present early in PHI, and that ART initiation during PHI resulted in only a partial shift of the epigenome to one with more favourable memory characteristics. These findings suggest that although ART initiation during PHI results in significant immune reconstitution, there may be only partial resolution of HIV-related phenotypic and epigenetic changes.https://www.frontiersin.org/articles/10.3389/fimmu.2021.647688/fullHIVT cellsPrimary HIV infection (PHI)Antiretroviral therapy (ART)Immune exhaustion |
| spellingShingle | Genevieve E. Martin Genevieve E. Martin Debattama R. Sen Debattama R. Sen Matthew Pace Nicola Robinson Jodi Meyerowitz Emily Adland John P. Thornhill John P. Thornhill Mathew Jones Ane Ogbe Lucia Parolini Natalia Olejniczak Panagiota Zacharopoulou Helen Brown Christian B. Willberg Christian B. Willberg Nneka Nwokolo Julie Fox Julie Fox Sarah Fidler Sarah Fidler W. Nicholas Haining W. Nicholas Haining John Frater John Frater Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy Frontiers in Immunology HIV T cells Primary HIV infection (PHI) Antiretroviral therapy (ART) Immune exhaustion |
| title | Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy |
| title_full | Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy |
| title_fullStr | Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy |
| title_full_unstemmed | Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy |
| title_short | Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy |
| title_sort | epigenetic features of hiv induced t cell exhaustion persist despite early antiretroviral therapy |
| topic | HIV T cells Primary HIV infection (PHI) Antiretroviral therapy (ART) Immune exhaustion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.647688/full |
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