A critical role for ICOS co-stimulation in immune containment of pulmonary influenza virus infection

Ian R. Humphreys, Lorna Edwards, Robert J. Snelgrove, Aaron J. Rae, Anthony J. Coyle, Tracy Hussell

    Research output: Contribution to journalArticlepeer-review


    Lung pathology observed during influenza infection is due to direct damage resulting from viral replication and bystander damage caused by overly exuberant antiviral immune mechanisms. In the absence of universally effective vaccines and antiviral therapies, knowledge of the cellular components required for immune containment of influenza is essential. ICOS is a late co-stimulatory molecule expressed by T cells 12-24 h after activation. We show for the first time that inhibition of ICOS with a monoclonal antibody reduces pulmonary T cell inflammation and associated cytokine expression. Surprisingly however, this reduction in T cells was not accompanied by an alleviation of weight loss and illness. Furthermore, lung viral titres were elevated following anti-ICOS treatment, suggesting that the beneficial outcome of reducing T cell pathology was masked by enhanced virus-induced damage and innate inflammation. This study demonstrates the delicate balance that exists between pathogen burden and pulmonary T cell inflammation during influenza infection and highlights the critical role of ICOS in this response. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Original languageEnglish
    Pages (from-to)2928-2938
    Number of pages10
    JournalEuropean journal of immunology
    Issue number11
    Publication statusPublished - Nov 2006


    • Co-stimulatory molecule
    • Influenza
    • Respiratory


    Dive into the research topics of 'A critical role for ICOS co-stimulation in immune containment of pulmonary influenza virus infection'. Together they form a unique fingerprint.

    Cite this