This project seeks to develop novel immunologic therapies for allergic diseases as well as the laboratory techniques required to understand their mechanism of action and rational application. We have developed a highly sensitive allergen specific T cell cytokine assay, which allows us a direct high throughput means to examine cytokine responses in clinical trials. Strategies that are being pursued include the administration of sIL-4 receptor as an anti-inflammatory/Th2 tolerogenic therapy for asthma. We are applying a similar approach to mouse vaccine models to understand how DNA vaccines generate specific immune responses.To date, we have examined the cytokine response to aeroallergens, demonstrating a uniform Th2 response in allergic asthmatics but little or no detectable response in healthy controls. Thus, the normal T cell response to aeroallergens is tolerance. This suggests that the therapeutic induction of tolerance to allergens may be an attractive strategy for the treatment of allergic asthma. A proposed phase I trial using rhIL-12 as an adjuvant in allergen immunotherapy was recently terminated for regulatory reasons. Antigen specific cytokine flow has been applied to DNA vaccination of mice, demonstrating that DNA vaccination creates a long lasting Th1 polarized immune response in both CD4-positive and CD8-positive subsets, whereas protein immunization generates a more transient response limited to CD4-positive T cells. - Asthma, allergy, T cells, tolerance, therapy, vaccine, Th2 cells, interleukin-4, blood, immunomodulation - Human Subjects
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