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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Delayed differentiation of potent effector CD8 + T cells reducing viremia and reservoir seeding in acute HIV infection
Science translational medicine, v 9(377)
15 Feb 2017
PMID: 28202771
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
CD8
T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8
T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8
T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8
T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8
T cells generated as early as AHI stages 1 and 2 before peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8
T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8
T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8
T cells contribute to the reduction of the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design interventions aiming at inducing these potent responses to cure HIV infection.
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Details
- Title
- Delayed differentiation of potent effector CD8 + T cells reducing viremia and reservoir seeding in acute HIV infection
- Creators
- Hiroshi Takata - Henry M. Jackson FoundationSupranee Buranapraditkun - Chulalongkorn UniversityCari Kessing - Scripps Research InstituteJames L K Fletcher - Thai Red Cross SocietyRoshell Muir - Drexel UniversityVirginie Tardif - Drexel UniversityPearline Cartwright - Case Western Reserve UniversityClaire Vandergeeten - Vaccine & Gene Therapy Institute of FloridaWendy Bakeman - Vaccine & Gene Therapy Institute of FloridaCarmen N Nichols - Vaccine & Gene Therapy Institute of FloridaSuteeraporn Pinyakorn - Henry M. Jackson FoundationPokrath Hansasuta - Chulalongkorn UniversityEugene Kroon - Thai Red Cross SocietyThep Chalermchai - Thai Red Cross SocietyRobert O'Connell - Armed Forces Research Institute of Medical ScienceJerome Kim - International Vaccine InstituteNittaya Phanuphak - SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, ThailandMerlin L Robb - Henry M. Jackson FoundationNelson L Michael - United States Military HIV Research ProgramNicolas Chomont - Centre Hospitalier de l’Université de MontréalElias K Haddad - Drexel UniversityJintanat Ananworanich - Henry M. Jackson FoundationLydie Trautmann - Henry M. Jackson FoundationRV254/SEARCH010 and the RV304/SEARCH013 Study Groups
- Publication Details
- Science translational medicine, v 9(377)
- Publisher
- American Association for the Advancement of Science (AAAS)
- Grant note
- R01 AI108433 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000394451100004
- Scopus ID
- 2-s2.0-85013399115
- Other Identifier
- 991019168098604721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Medicine, Research & Experimental