The role of CRTH2 + CD8 + T cells in severe asthma

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Keywords: Immunology & Infectious diseaseThe immune responses causing severe asthma have been defined as possessing a ""type 2"" cytokine bias. These cytokines, which include interleukins 4, 5,and 13 are secreted by lymphoid subsets and attract the classic eosinophilic infiltrates associated with the disease. We have recently found that in human disease a potent source of these cytokines in the lung is the CD8+ T cell compartment. CD8+ T cells which secrete type 2 cytokines express the molecule CRTH2, a functional receptor for PGD2 (prostaglandin D2) and are the most enriched in disease, including in the lung. This is a surprising and novel result (manuscript in preparation) and suggests they may play a critical role in disease pathogenesis. Using samples obtained from patients with severe asthma and controls, this project will address: The full functional capacity of Tc2 cells in response to distinct stimuli The functional interactions of Tc2 cells with epithelial cells and eosinophils and their localisation in situ heir specificity, by analysis of TCR and response to specific antigens. The project uses basic science approaches combined with careful clinical sampling to address an important health issue. Tc2 cells likely have a role in other inflammatory diseases, infections and also cancers (such as pancreatic cancer), so defining their activity has broad implications and depending on progress, other disease areas will be explored."