title: Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection.
abstract: While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. We performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do not contain high levels of cytolytic markers, and exhibit low levels of activation and proliferation, representing distinct properties from CD8(+) T cells associated with HIV-1 control. These data reveal the potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection.
authors.affiliation: Medical Research Council (United Kingdom) Laboratories The Gambia, Fajara, The Gambia, West Africa. thushandesilva@hotmail.com
authors.forename: Thushan I
authors.initials: TI
authors.lastname: de Silva
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Peng
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Leligdowicz
authors.forename: Irfan
authors.initials: I
authors.lastname: Zaidi
authors.forename: Lucy
authors.initials: L
authors.lastname: Li
authors.forename: Harry
authors.initials: H
authors.lastname: Griffin
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Blais
authors.forename: Tim
authors.initials: T
authors.lastname: Vincent
authors.forename: Mavinga
authors.initials: M
authors.lastname: Saraiva
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Yindom
authors.forename: Carla
authors.initials: C
authors.lastname: van Tienen
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D014766:Viremia / Q000188:drug therapy / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; C114505:CD160 protein, human; C084093:CD244 protein, human; D058851:GPI-Linked Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D054301:gag Gene Products, Human Immunodeficiency Virus