Developmental Immunotherapeutics For Allergic Diseases

该项目旨在开发用于过敏性疾病的新型免疫疗法，以及了解其作用机制和合理应用所需的实验室技术。我们已经开发了使用流式细胞术和真实的时间定量PCR两者来直接测量过敏原特异性T细胞应答的方法，其灵敏度和保真度在此之前是不可能的。我们目前正在进行一项临床试验，检查过敏原免疫治疗的免疫学效果，使用这些测定。这项工作的假设是过敏原免疫疗法通过耐受性（过敏原特异性T细胞的减少）而不是通过Th 2向Th 1的转变起作用。了解过敏原免疫治疗的免疫学机制是开发新的更有效的抗原特异性治疗的必要条件。 IL-10用于银屑病关节炎的30天II期临床试验，以检查其抗炎和免疫调节作用。与安慰剂相比，IL-10治疗与皮肤改善有关，但与关节疾病无关。IL-10给药引起单核因子和Th 1细胞因子产生的下调，但与记忆/效应（Th 1/Th 2）亚群频率的变化无关。

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.