The influence of viral infection on therapeutic immune tolerance in allergic airways disease.

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Allergic airways disease such as asthma is rising in children. Allergy can be triggered by different environmental allergens (e.g. pollen). In susceptible children, inhaling allergens may cause allergic reactions with breathing problems, sometimes requiring hospital treatment. Treatment with small allergen fragments, called peptide-based immunotherapy (PIT), can render allergic patients tolerant, i.e. unresponsive to their allergen, without the risk of allergic reactions. How tolerance to allergen develops is not fully understood. Children commonly suffer from viral infections such as the common cold and can sometimes develop allergic airways disease thereafter. Why this happens is unclear, but it is thought that viral infections interfere with the immune cells that maintain tolerance. Thus, there is concern that PIT may be ineffective or even detrimental if it coincides with a viral infection. Using a mouse model, I will study how immune cells contribute to the development of tolerance following PIT. I will then determine the effects of viral infection both on these cells and on the ability of PIT to induce tolerance. Understanding these interactions is vital if PIT is to be used safely in treating children with allergy. In addition, my studies will further our understanding of the mechanisms underlying virus induced allergy.