title: HIV "elite controllers" are characterized by a high frequency of memory CD8+ CD73+ T cells involved in the antigen-specific CD8+ T-cell response.
abstract: Human immunodeficiency virus type 1 (HIV-1) infection is characterized by chronic immune activation and suppressed T-lymphocyte functions. Here we report that CD73, both a coactivator molecule of T cells and an immunosuppressive ecto-enzyme through adenosine production, is only weakly expressed by CD8+ T cells of HIV-infected patients and only partially restored after successful antiviral treatment. CD73 expression on CD8+ T cells correlates inversely with cell activation both ex vivo and in vitro. However, CD8+ T cells from HIV controllers (HICs), which spontaneously control HIV replication, express CD73 strongly, despite residual immune activation. Finally, we demonstrate that CD73 is involved in the HIV-specific CD8+ T-cell expansion. Thus, we show that CD73 is central to the functionality of HIV-specific CD8+ T cells and that the preservation of HIV-specific CD73+ CD8+ T cells is a characteristic of HICs. These observations reveal a novel mechanism involved in the control of viral replication.
authors.affiliation: INSERM U955, Equipe 16, Créteil.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Carrière
authors.forename: Christine
authors.initials: C
authors.lastname: Lacabaratz
authors.forename: Ayrin
authors.initials: A
authors.lastname: Kök
authors.forename: Clarisse
authors.initials: C
authors.lastname: Benne
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.forename: Sophie
authors.initials: S
authors.lastname: Hüe
authors.forename: Laurent
authors.initials: L
authors.lastname: Hocqueloux
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelièvre
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
mesh_terms: D015720:5'-Nucleotidase / Q000097:blood / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D058851:GPI-Linked Proteins / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans
chemical_list: D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human
keywords: CD73; CD8+ T-cell response; HIV; HIV controller; activation