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

First Author  Humphreys IR Year  2006
Journal  Eur J Immunol Volume  36
Issue  11 Pages  2928-38
PubMed ID  17039567 Mgi Jnum  J:116989
Mgi Id  MGI:3695344 Doi  10.1002/eji.200636155
Citation  Humphreys IR, et al. (2006) A critical role for ICOS co-stimulation in immune containment of pulmonary influenza virus infection. Eur J Immunol 36(11):2928-38
abstractText  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.
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