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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Bluetongue virus (BTV) is an arthropod-borne <jats:italic>Orbivirus<\/jats:italic> that is almost solely transmitted by <jats:italic>Culicoides<\/jats:italic> biting midges and causes a globally important haemorrhagic disease, bluetongue (BT), in susceptible ruminants. Infection with BTV is characterised by immunosuppression and substantial lymphopenia at peak viraemia in the host.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, the role of cell-mediated immunity and specific T-cell subsets in BTV pathogenesis, clinical outcome, viral dynamics, immune protection, and onwards transmission to a susceptible <jats:italic>Culicoides<\/jats:italic> vector is defined in unprecedented detail for the first time, using an <jats:italic>in vivo<\/jats:italic> arboviral infection model system that closely mirrors natural infection and transmission of BTV. Individual circulating CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>, or WC1<jats:sup>+<\/jats:sup> \u03b3\u03b4 T-cell subsets in sheep were depleted through the administration of specific monoclonal antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The absence of cytotoxic CD8<jats:sup>+<\/jats:sup> T cells was consistently associated with less severe clinical signs of BT, whilst the absence of CD4<jats:sup>+<\/jats:sup> and WC1<jats:sup>+<\/jats:sup> \u03b3\u03b4 T cells both resulted in an increased clinical severity. The absence of CD4<jats:sup>+<\/jats:sup> T cells also impaired both a timely protective neutralising antibody response and the production of IgG antibodies targeting BTV non-structural protein, NS2, highlighting that the CD4<jats:sup>+<\/jats:sup> T-cell subset is important for a timely protective immune response. T cells did not influence viral replication characteristics, including onset\/dynamics of viraemia, shedding, or onwards transmission of BTV to <jats:italic>Culicoides<\/jats:italic>. We also highlight differences in T-cell dependency for the generation of immunoglobulin subclasses targeting BTV NS2 and the structural protein, VP7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study identifies a diverse repertoire of T-cell functions during BTV infection in sheep, particularly in inducing specific anti-viral immune responses and disease manifestation, and will support more effective vaccination strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1328820","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T04:27:25Z","timestamp":1706675245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Specific T-cell subsets have a role in anti-viral immunity and pathogenesis but not viral dynamics or onwards vector transmission of an important livestock 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