DEVELOPMENTAL IMMUNOTHERAPEUTICS FOR ALLERGIC DISEASES AND ASTHMA

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。我们已经开发了一种高灵敏度的过敏原特异性T细胞细胞因子测定，这使我们能够直接高通量的手段来检查临床试验中的细胞因子反应。正在实施的策略包括施用sIL-4受体作为哮喘的抗炎/Th 2耐受原性疗法。我们正在将类似的方法应用于小鼠疫苗模型，以了解DNA疫苗如何产生特异性免疫应答。迄今为止，我们已经研究了对空气过敏原的细胞因子应答，证明了过敏性哮喘患者的Th 2应答是一致的，但在健康对照组中几乎没有或检测不到应答。因此，正常的T细胞对空气过敏原的反应是耐受性。这表明对过敏原的耐受性的治疗诱导可能是治疗过敏性哮喘的一个有吸引力的策略。一项使用rhIL-12作为过敏原免疫治疗佐剂的I期试验最近因监管原因而终止。抗原特异性细胞因子流已应用于小鼠的DNA疫苗接种，证明DNA疫苗接种在CD 4阳性和CD 8阳性亚群中产生持久的Th 1极化免疫应答，而蛋白质免疫产生限于CD 4阳性T细胞的更短暂的应答。- 哮喘，过敏，T细胞，耐受性，治疗，疫苗，Th 2细胞，白细胞介素-4，血液，免疫调节-人类受试者

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