Rhinovirus infection augments recruitment of Th2 allergen specific T cells to the airway

Session IV – Walton, Ross – Young Investigator Applicant

Title of Contribution: Rhinovirus infection augments recruitment of Th2 allergen specific T cells to the airway
Author(s): Ross P Walton, Nathan W Bartlett, Sebastian L Johnston
Affiliation(s): Department of Respiratory Medicine, Imperial College London. UK

Abstract:

Respiratory viral infections are the major precipitant of asthma exacerbations in both children and adults, with rhinovirus (RV) highlighted as being the most important pathogen involved. Whilst it is accepted that virus and allergen act together in synergy to give rise to exacerbations, the mechanisms underlying this synergistic relationship are poorly understood. To investigate this interaction we use a novel mouse model of rhinovirus infection. We show that viral infection enhances the recruitment of adoptively transferred allergen specific CD4+ Th2 cells into the airway. Furthermore, virus infection enhanced lung leukocyte production of IL-4. Naïve allergen specific CD4+ T cells from DO11.10 OVA transgenic mice were polarized to a Th2 phenotype and expanded in culture.  Allergen specific IL-4 producing CD4+ T cells were then transferred into naïve BALB/c mice intraperitoneally. Mice were then challenged with OVA intranasally (i.n.) on days 2,3 and 4 post cell transfer (controls receiving PBS). On the final challenge mice we infected with RV i.n. (UV inactivated-RV for controls). Groups were as follows: OVA challenged and RV infection (RV-OVA), OVA challenged and UV-RV infected (UV-OVA), PBS challenged and RV infected (RV-PBS) and PBS challenged and UV-RV infected (UV-PBS). Allergen challenged RV infected animals (RV-OVA) had increased eosinophilic infiltration into the bronchoalveolar lavage (BAL) at days 2 and 6 post infection compared with UV-OVA or RV-PBS groups, indicative of a allergic type response. Similar lymphocyte numbers were observed in both RV-OVA and RV-PBS. Flow cytometric analysis of the T cell population in the lung draining lymph nodes revealed comparable numbers of OVA-specific CD4+T cells present in RV-OVA and UV-OVA groups at day 2, however, at day 6 post–infection a 40% percent reduction in these cells was observed in the RV-OVA group only. At this same time point the number of OVA-specific CD4+ T cells in the BAL of the RV-OVA animals was 2 fold higher than UV-OVA or RV-PBS animals. This cell profile is suggestive of a pronounced migration of allergen specific T cells from the lymph node to the airway following viral infection and allergen challenge, whilst in the absence of a viral infection the allergen specific T cells remain in the mediastinal lymph nodes. In addition, levels of IL-4 production in lung leukocytes in response to OVA stimulation was were increased 2 fold in RV-OVA groups at day 6 post-infection. This data highlights a role for respiratory viral infection not only in enhancing recruitment of allergen specific T cells into the airway but in addition augmenting the production of Type 2 cytokines in an allergen specific manor in the lung, a potential mechanism for the viral exacerbation of allergic airway disease and asthma.