Allergen-specific lung resident CD4+ Th2 cells in asthma (HYP4P.417)

Abstract

Abstract Asthma is an inflammatory disease of the airways that affects more than 300 million people worldwide. Clinically, asthma is characterized by acute, intermittent and recurrent episodes of inflammation that can be induced by a specific allergen. Allergen-specific CD4 T cells contribute to this process by producing cytokines and inducing B lineage production of IgE. Allergen-specific CD4 memory T cells are also thought to persist after resolution of inflammation to rapidly drive asthma-induced pathology. Due to the challenge of tracking small populations of CD4 T cells that express allergen pMHCII-specific TCRs, little is known about what regulates Th2 memory cell differentiation, migration and maintenance. We have therefore produced a MHCII tetramer containing a peptide from the Derp1 protein of the house dust mite (HDM), the most common cause of atopic asthma, to elucidate the underlying mechanisms of Th2 memory cell differentiation during atopic asthma. Tetramer-based enrichment strategies used to isolate Derp1:I-Ab+ cells from the secondary lymphoid organs and lungs have revealed that heterogenous Th2 memory populations form, including a CD69+ Derp1:I-Ab+ population in the lung thats persists post-contraction. Intravascular staining techniques demonstrate that these cells reside in the lung parenchyma and are driven to the lung by early cytokine exposure. These findings have important implications for novel immunotherapeutics in both asthma and allergy.