Gamma Delta T Cells Regulate the Inflammatory Response to Rhinovirus Infection.

Abstract

Rationale: Human rhinoviruses (HRV) cause the common cold and are associated with more severe respiratory disease as precipitants of asthma exacerbations. The mechanisms underlying HRV induced asthma exacerbation however remain unclear. γδ T cells have been implicated as important modulators of antiviral immunity and as regulators of allergic airways disease. Using a mouse model we have characterised lung lymphocyte responses following HRV infection and demonstrated that γδ T cells are recruited from day 2 post infection. We hypothesised that these cells would contribute to the pro inflammatory antiviral phenotype induced by HRV infection in vivo. Methods: BALB/c mice were infected intranasally with RV1B or UV inactivated RV1B. γδ T cells were depleted by intraperitoneal injection of anti−TCRδ or isotype control antibody at days −1 and +3 post infection. Bronchioalveolar lavage (BAL) and lung cell populations were enumerated on differentially stained cytospins or by flow cytometry. BAL chemokines were measured by ELISA. Viral RNA in lung tissue was measured by Taqman real time PCR and airway hyperreactivity (AHR) was evaluated in response to methacholine challenge using whole body plethysmography. Results: The immune response to HRV infection was characterised by neutrophilic and lymphocytic airway inflammation. The lymphocyte response was Th1 orientated and comprised CD4, CD8, and γδ TCR+ cells. Depletion of γδ cells resulted in enhanced BAL neutrophilia (1.5−2 fold increase) and inflammatory cytokine/chemokine production at 24hrs post infection. In depleted mice enhanced neutrophilia was associated with decreased HRV RNA and IFN−beta mRNA in the lung at day 2 as well as a trend toward enhanced AHR at 24hrs. Conclusions: γδ T cells regulate the inflammatory response to HRV infection, limiting leukocyte recruitment to the airway and AHR. However, downmodulation of early inflammatory responses may lead to impaired control of viral replication. This abstract is funded by: Imperial College.