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Journal article
Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection
Blood, v 120(17), pp 3466-3477
25 Oct 2012
PMID: 22955926
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Immediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.
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Details
- Title
- Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection
- Creators
- Lydie Trautmann - University of MiamiFlorentin-Martial Mbitikon-Kobo - Vaccine & Gene Therapy Institute of FloridaJean-Philippe Goulet - Université de MontréalYoav Peretz - Caprion/ImmuneCarta Services, Montréal, QC; andYu Shi - Vaccine & Gene Therapy Institute of FloridaJulien Van Grevenynghe - Vaccine & Gene Therapy Institute of FloridaFrancesco Andrea Procopio - Vaccine & Gene Therapy Institute of FloridaMohamad Rachid Boulassel - McGill University Health CentreJean-Pierre Routy - McGill University Health CentreNicolas Chomont - University of MiamiElias K. HaddadRafick-Pierre Sekaly - University of Miami
- Publication Details
- Blood, v 120(17), pp 3466-3477
- Publisher
- American Society of Hematology
- Grant note
- National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000311623800013
- Scopus ID
- 2-s2.0-84868534523
- Other Identifier
- 991020100077604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Hematology