title: Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection.
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.
authors.affiliation: Division of Infectious Diseases, Vaccine and Gene Therapy Institute-Florida, Port Saint Lucie, USA. ltrautmann@vgtifl.org
authors.forename: Lydie
authors.initials: L
authors.lastname: Trautmann
authors.forename: Florentin-Martial
authors.initials: FM
authors.lastname: Mbitikon-Kobo
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Goulet
authors.forename: Yoav
authors.initials: Y
authors.lastname: Peretz
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Julien
authors.initials: J
authors.lastname: Van Grevenynghe
authors.forename: Francesco Andrea
authors.initials: FA
authors.lastname: Procopio
authors.forename: Mohamad Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
mesh_terms: D000208:Acute Disease; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000276:immunology*; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D019562:Viral Load
chemical_list: D007376:Interleukin-2; D020395:Receptors, Interleukin-7; D007371:Interferon-gamma