Establishing potential mechanisms by which viral infection exacerbates asthma 4206

Abstract Description Respiratory viruses are the leading cause of asthma exacerbations, accounting for approximately 80% of exacerbations. Previous studies have demonstrated a significant increase in total CD4+ T cells in the lung as well as increased production of IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid during viral exacerbations. Although these findings suggest a central role for Th2 cells, the specific T cell subset responsible for driving the exacerbation has not been identified. This study aims to elucidate the mechanism by which respiratory viral infections can elicit a type II cytokine environment. Specifically, we seek to characterize the T cell subset driving viral exacerbations of asthma. To evaluate the expansion of an antigen-specific Th2 population during viral exacerbations and assess the Th1/Th2 ratio in the lung, we optimized a mixed allergen model. In this model, congenically marked OT-II cells are adoptively transferred into host mice, which are subsequently challenged with a mixture of house dust mite and ovalbumin. This approach recapitulates key features of asthma, including increased eosinophilia and IL-4 production. Using this model, we can examine the Th1/Th2 ratio among endogenous cells and track the expansion of transferred OT-II cells in response to subsequent infection with influenza A/PR/8/34. This model provides a platform for dissecting the cellular mechanisms underlying viral exacerbations of asthma. Funding Sources National Jewish Health Murnick Asthma Discovery Accelerator Program; Viola Vestal Coulter Foundation Fellowship Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)