CD8+ T Cells Complement Antibodies in Protecting against Yellow Fever Virus

Maria R Bassi, Michael Kongsgaard, Maria A Steffensen, Christina Fenger, Michael Rasmussen, Karsten Skjødt, Bente Finsen, Anette Stryhn, Søren Buus, Jan P Christensen, Allan R Thomsen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Abstract

    The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo.

    OriginalsprogEngelsk
    TidsskriftJournal of Immunology
    Vol/bind194
    Udgave nummer3
    Sider (fra-til)1141-1153
    ISSN0022-1767
    DOI
    StatusUdgivet - 1. feb. 2015

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