title: Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection.
abstract: Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57-), and more frequently produced IFN-gamma or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-gamma+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4+ T cell response that is associated with delayed disease progression in the majority of infected people.
authors.affiliation: Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Melody G
authors.initials: MG
authors.lastname: Duvall
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Alabi
authors.forename: David J
authors.initials: DJ
authors.lastname: Jeffries
authors.forename: Marianne
authors.initials: M
authors.lastname: van der Sande
authors.forename: Toyin O
authors.initials: TO
authors.lastname: Togun
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: McConkey
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Hilton C
authors.initials: HC
authors.lastname: Whittle
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018959:CD57 Antigens / Q000096:biosynthesis / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000821:virology
chemical_list: D018959:CD57 Antigens; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D007376:Interleukin-2; D007371:Interferon-gamma