RESPIRATORY INFECTION

Healthy but not RSV-infected lung epithelial cells profoundly inhibit T cell activation

H Wang^1,2, Z Su^1,3, J Schwarze^1,2

¹ Department of Respiratory Medicine, National Heart and Lung Institute and Wright Fleming Institute of Infection and Immunity, Imperial College London, UK
² Child Life and Health and Centre for Inflammation Research, University of Edinburgh, UK
³ Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, China

Professor J Schwarze, Child Life and Health, and Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; jurgen.schwarze{at}ed.ac.uk

Background: Respiratory viruses, including respiratory syncytial virus (RSV), can cause asthma exacerbations and bronchiolitis. Both conditions are associated with enhanced cognate immune responses and inflammation and reduced immune regulation. Lung epithelial cells (LECs) can contribute to antiviral and allergic immune responses while gut epithelial cells can inhibit effector T cell responses. A study was performed to determine whether healthy LECs regulate antigen-specific T cell responses and if this regulation is lost during RSV infection.

Methods: LA4 cells, a murine LEC line, infected with RSV or primary murine LECs were co-cultured with ovalbumin-specific T cell receptor transgenic CD4+ T cells from DO11.10 mice and ovalbumin-pulsed bone marrow-derived dendritic cells (DC) to assess T cell proliferation by flow cytometry and cytokine production.

Results: The presence of LECs abrogated DC-induced T cell proliferation and significantly reduced T cell cytokine release. These effects of LECs were predominantly contact-dependent, primarily affected T cells directly and were partly mediated by transforming growth factor β. Soluble factors and DC-mediated effects also contributed to T cell inhibition. RSV infection of LECs reduced their inhibitory capacity in an infection dose-dependent manner. This was independent of proinflammatory cytokines released by infected LECs, but in part due to Toll-like receptor activation and to infection-induced cell death.

Conclusion: Healthy LECs are potent inhibitors of T cell activation, but this regulatory function is lost after RSV infection. These findings suggest a central role for LECs in maintaining the tolerogenic environment of healthy lungs. Loss of this regulatory capacity after viral infection may allow development of excessive cognate immune responses and pulmonary inflammation.

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This article has been cited by other articles:

• Brodlie, M, Eger, K, Hilkens, C M U, Ward, C (2009). Airway epithelial cells as guardians of immune homeostasis?. Thorax 64: 1009-1009 [Full Text]  
• Smyth, R. L (2009). The airway epithelium in health and disease: "calm on the surface, paddling furiously underneath". Thorax 64: 277-278 [Full Text]