title: HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype.
abstract: Some rare HIV-1-infected individuals, referred to as HIV controllers (HIC), have persistently undetectable plasma viral load in the absence of therapy. This control of HIV-1 replication has been associated with a strong, multifunctional specific CD8(+) T cell response. However, no direct link between this immune response and the control of viremia has so far been provided. We investigated parameters of specific CD8(+) T cell response and in vitro susceptibility to HIV-1 infection in 11 HIC. We found high frequencies of HIV-specific CD8(+) T cells. Interestingly, these cells expressed the activation marker HLA-DR but not CD38. This unique phenotype differentiates HIV-specific CD8(+) T cells from HIC and noncontroller subjects and likely reflects a high potential to expand upon exposure to antigen and a capacity to exert effector functions. Accordingly, although CD4(+) T cells from HIC were fully susceptible to HIV-1 superinfection, their CD8(+) T cells effectively suppressed HIV-1 infection. Remarkably, this potent anti-HIV activity was observed without prior stimulation of CD8(+) T cells. This activity was not mediated by secreted inhibitory factors but was due to the elimination of infected CD4(+) T cells and was observed only with autologous CD4(+) T cells, indicating an HLA-restricted cytotoxic mechanism. This constitutive antiviral capacity of CD8(+) T cells could account for the control of viral replication in HIC.
authors.affiliation: Unité de Régulation des Infections Rétrovirales, Institut Pasteur, 75725 Paris, France.
authors.forename: Asier
authors.initials: A
authors.lastname: Sáez-Cirión
authors.forename: Christine
authors.initials: C
authors.lastname: Lacabaratz
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Pierre
authors.initials: P
authors.lastname: Versmisse
authors.forename: Alejandra
authors.initials: A
authors.lastname: Urrutia
authors.forename: Faroudy
authors.initials: F
authors.lastname: Boufassa
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Martine
authors.initials: M
authors.lastname: Sinet
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.forename: Alain
authors.initials: A
authors.lastname: Venet
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology