Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques |
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Authors: | Hryniewicz Anna Price David A Moniuszko Marcin Boasso Adriano Edghill-Spano Yvette West Sadie M Venzon David Vaccari Monica Tsai Wen-Po Tryniszewska Elzbieta Nacsa Janos Villinger Francois Ansari Aftab A Trindade Christopher J Morre Michel Brooks David Arlen Philip Brown Helen J Kitchen Christina M R Zack Jerome A Douek Daniel C Shearer Gene M Lewis Mark G Koup Richard A Franchini Genoveffa |
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Affiliation: | Animal Models and Retroviral Vaccines Section, National Cancer Institute, Building 41, Bethesda, MD 20892, USA. |
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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. |
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