A critical role for ICOS co-stimulation in immune containment of pulmonary influenza virus infection.
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.
Humphreys
Ian R
IR
Centre for Molecular Microbiology and Infection, Department of Biochemistry, Imperial College, London, UK.
Edwards
Lorna
L
Snelgrove
Robert J
RJ
Rae
Aaron J
AJ
Coyle
Anthony J
AJ
Hussell
Tracy
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D060889:Inducible T-Cell Co-Stimulator Protein; D009980:Influenza A virus / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein