Mechanisms of Allergen Immunotherapy

Asthma is a major public health problem due to its high prevalence and significant impact on activities of daily living. Allergen immunotherapy or vaccination consists of the therapeutic administration of allergen extract. The efficacy of allergen immunotherapy in asthma is modest, however immunotherapy remains the only known disease modifying therapy for allergic asthma. Because the exact mechanism through which immunotherapy works is unclear, a greater understanding of the mechanism of action of allergen immunotherapy is needed before modern immunopharmacologic methods can be applied to increase its therapeutic efficacy. This goal of the study is to determine the effects of allergen immunotherapy on allergen specific T cell responses. This is an open label study in which allergen specific CD4+T lymphocyte responses will be monitored before, during and after 12 weekly injections of maintenance immunotherapy, allowing the study of both the induction as well as decay of these changes. Immunotherapy will be employed in a rush/cluster schedule consisting of the serial administration of rapidly increasing doses of allergen delivered subcutaneously over a 2 day period (rush), followed by more gradually increasing weekly injections over 2-6 weeks (cluster), during which time the subject is brought to a maintenance allergen dose, which will then be repeatedly administered on a weekly basis. Immunological endpoints will consist of the frequency and cytokine profile of allergen specific T cell responses as measured by intracellular cytokine staining and the measurement of in vitro induced T cell cytokines by real time RT-PCR. Ten allergic asthmatic subjects will be enrolled in the therapeutic arm of the study.