title: Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication.
abstract: "Elite controllers" are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals' CD8+ cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8+ cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8+ T cells expanded up to 2,500-fold above pre-depletion levels. This wave of CD8+ T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8+ NK cell frequencies changed no more than threefold. Together, our data suggest that CD8+ T cells targeting a small number of epitopes, along with broad CD4+ T-cell responses, can successfully control the replication of the AIDS virus. It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control.
authors.affiliation: Wisconsin National Primate Research Center, 1220 Capitol Court, Madison, WI 53715-1299, USA. thomasf@primate.wisc.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: Laura E
authors.initials: LE
authors.lastname: Valentine
authors.forename: Levi J
authors.initials: LJ
authors.lastname: Yant
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.forename: Shari M
authors.initials: SM
authors.lastname: Piaskowski
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Furlott
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Weisgrau
authors.forename: Benjamin
authors.initials: B
authors.lastname: Burwitz
authors.forename: Gemma E
authors.initials: GE
authors.lastname: May
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: León
authors.forename: Taeko
authors.initials: T
authors.lastname: Soma
authors.forename: Gnankang
authors.initials: G
authors.lastname: Napoe
authors.forename: Saverio V
authors.initials: SV
authors.lastname: Capuano
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D014644:Genetic Variation / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag