title: Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers.
abstract: BACKGROUND
  HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status.
  
  
  METHODS
  We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated.
  
  
  RESULTS
  Compared to CD38+/HLA-DR+ cells, CD38-/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134-462] vs 638 [307-747], P = 0.001), higher frequency of polyfunctional cells (15% [7%-33%] vs 21% [16%-43%], P = 0.0003), greater proliferative capacity (0-fold [0-2] vs 3-fold [2]-[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%-11%] vs 13% [6%-22%], P = 0.02). The CD38-/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations.
  
  
  CONCLUSIONS
  These data highlight the role of CD38-/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies.
authors.affiliation: INSERM U1012, Le Kremlin-Bicêtre, France; Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hua
authors.affiliation: INSERM U1012, Le Kremlin-Bicêtre, France; Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Lécuroux
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Asier
authors.initials: A
authors.lastname: Sáez-Cirión
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.affiliation: INSERM U1012, Le Kremlin-Bicêtre, France; Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Girault
authors.affiliation: Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Versmisse
authors.affiliation: Université Paris-Sud 11, Le Kremlin-Bicêtre, France; INSERM U1018, Le Kremlin-Bicêtre, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Département d'épidémiologie, Le Kremlin-Bicêtre, France.
authors.forename: Faroudy
authors.initials: F
authors.lastname: Boufassa
authors.affiliation: AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Taulera
authors.affiliation: INSERM U1012, Le Kremlin-Bicêtre, France; Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Sinet
authors.affiliation: INSERM U1012, Le Kremlin-Bicêtre, France; Université Paris-Sud 11, Le Kremlin-Bicêtre, France; AP-HP, Hôpital Bicêtre, Service de Médecine Interne, Le Kremlin-Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: INSERM U1012, Le Kremlin-Bicêtre, France; Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Venet
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D051997:ADP-ribosyl Cyclase 1