Developmental Immunotherapeutics For Allergic Diseases

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Abstract

This project seeks to develop novel immunologic therapies for allergic diseases as well as the laboratory techniques required to understand their mechanisms of action and rational application. We have developed the means, using both flow cytometry and real time quantitative PCR to directly measure allergen specific T cell responses with a sensitivity and fidelity heretofore not possible. We are presently performing a clinical trial examining the immunological effects of allergen immunotherapy using these assays. The hypothesis of this work is that allergen immunotherapy works via tolerance (a decrease in allergen specific T cells) rather than via a Th2 to Th1 shift. Understanding the immunological mechanisms of allergen immunotherapy is a requisite for developing new more effective antigen specific therapies. IL-10 was used in a 30 day phase II clinical trial in psoriatic arthritis to examine its' anti-inflammatory and immunomodulatory effects. IL-10 therapy was associated with improvements in skin but not joint disease, relative to placebo. IL-10 administration caused a down regulation of monokine and Th1 cytokine production, but was not associated with changes in the frequencies of memory/effector (Th1/Th2) subsets.