title: Polyfunctional T cell responses are a hallmark of HIV-2 infection.
abstract: HIV-2 is distinguished clinically and immunologically from HIV-1 infection by delayed disease progression and maintenance of HIV-specific CD4(+) T cell help in most infected subjects. Thus, HIV-2 provides a unique natural human model in which to investigate correlates of immune protection against HIV disease progression. Here, we report a detailed assessment of the HIV-2-specific CD4(+) and CD8(+) T cell response compared to HIV-1, using polychromatic flow cytometry to assess the quality of the HIV-specific T cell response by measuring IFN-gamma, IL-2, TNF-alpha, MIP-1beta, and CD107a mobilization (degranulation) simultaneously following Gag peptide stimulation. We find that HIV-2-specific CD4(+) and CD8(+) T cells are more polyfunctional that those specific for HIV-1 and that polyfunctional HIV-2-specific T cells produce more IFN-gamma and TNF-alpha on a per-cell basis than monofunctional T cells. Polyfunctional HIV-2-specific CD4(+) T cells were generally more differentiated and expressed CD57, while there was no association between function and phenotype in the CD8(+) T cell fraction. Polyfunctional HIV-specific T cell responses are a hallmark of non-progressive HIV-2 infection and may be related to good clinical outcome in this setting.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Melody G
authors.initials: MG
authors.lastname: Duvall
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Precopio
authors.forename: David A
authors.initials: DA
authors.lastname: Ambrozak
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Hilton C
authors.initials: HC
authors.lastname: Whittle
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte