title: Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques.
abstract: The loss of CD4(+) T cells and the impairment of CD8(+) T cell function in HIV infection suggest that pharmacological treatment with IL-7 and IL-15, cytokines that increase the homeostatic proliferation of T cells and improve effector function, may be beneficial. However, these cytokines could also have a detrimental effect in HIV-1-infected individuals, because both cytokines increase HIV replication in vitro. We assessed the impact of IL-7 and IL-15 treatment on viral replication and the immunogenicity of live poxvirus vaccines in SIV(mac251)-infected macaques (Macaca mulatta). Neither cytokine augmented the frequency of vaccine-expanded CD4(+) or CD8(+) memory T cells, clonal recruitment to the SIV-specific CD8(+) T cell pool, or CD8(+) T cell function. Vaccination alone transiently decreased the viral set point following antiretroviral therapy suspension. IL-15 induced massive proliferation of CD4(+) effector T cells and abrogated the ability of vaccination to decrease set point viremia. In contrast, IL-7 neither augmented nor decreased the vaccine effect and was associated with a decrease in TGF-beta expression. These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals.
authors.affiliation: Animal Models and Retroviral Vaccines Section, National Cancer Institute, Building 41, Bethesda, MD 20892, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Hryniewicz
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.forename: Adriano
authors.initials: A
authors.lastname: Boasso
authors.forename: Yvette
authors.initials: Y
authors.lastname: Edghill-Spano
authors.forename: Sadie M
authors.initials: SM
authors.lastname: West
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.forename: Wen-Po
authors.initials: WP
authors.lastname: Tsai
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Janos
authors.initials: J
authors.lastname: Nacsa
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Trindade
authors.forename: Michel
authors.initials: M
authors.lastname: Morre
authors.forename: David
authors.initials: D
authors.lastname: Brooks
authors.forename: Philip
authors.initials: P
authors.lastname: Arlen
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Brown
authors.forename: Christina M R
authors.initials: CM
authors.lastname: Kitchen
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Gene M
authors.initials: GM
authors.lastname: Shearer
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014766:Viremia / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D019409:Interleukin-15; D015851:Interleukin-7; D018449:SAIDS Vaccines; D016212:Transforming Growth Factor beta