HUMAN DENDRITIC CELLS, ALLERGY AND ASTHMA

树突状细胞(DC)被认为是主要抗原(Ag)。 呈现细胞。这些细胞的生物学及其在人类中的作用 健康和疾病中的免疫反应还没有被研究过 由于难以获得大量这样的信息而导致的深度 外周血中的细胞和无法培养这些细胞 体外培养。最近由PI和其他人进行的实验表明 从外周血中大量获取DC是可行的 随着分离程序的改进和GM-CSF和 IL-4。屋尘螨(HDM)引起的哮喘是一种主要的公共卫生问题 问题和过敏反应被认为是由 长期接触低剂量的HDM变应原。银 呈递细胞在变态反应性疾病的发展中起着关键作用。 这个实验室和其他实验室的结果显示，在相同的银 两种专业抗原提呈细胞类型DC和B细胞的诱导 T辅助细胞子集不同。DC偏爱Th1，而B细胞处于低水平 AG浓度有利于Th2应答。美国政府的扭曲反应 Th2亚群是引起过敏性疾病的原因之一。考察……的基础 DC和B细胞对T辅助细胞亚群的相反刺激作用 细胞方面，提出了以下具体目标：(I)从 外周血以确定影响生存的因素 和增殖潜能；(2)确定其机制 哮喘患者与正常人T辅助细胞亚群应答的差异 个人；以及(3)确定T细胞表位 DC或由Ag呈现生成的两个不同的T辅助子集 B细胞。拟议的实验将为这一角色提供新的见解 可能为哮喘患者DC的设计提供合理的依据。 过敏性疾病的免疫治疗。

Dendritic cells (DC) are considered to be the major antigen (Ag) presenting cells. The biology of these cells and their role in the human immune response in both health and disease have not been studied in depth due to the difficulty in obtaining a significant number of these cells from peripheral blood and the inability to culture these cells in vitro. Recent experiments carried out by the PI and by others indicate it is feasible to obtain a large number of DC from peripheral blood with improved isolation procedures and the addition of GM-CSF and IL-4. House dust mite (HDM)-induced asthma is a major public health problem and the allergic response is considered to be initiated by exposure to low doses of HDM allergens over a prolonged period. Ag presenting cells play critical roles in allergy disease development. Results from this laboratory and others showed that with the same Ag the two professional Ag presenting cell types DC and B cells induced T helper cell subsets differently. DC favor Th1 whereas B cells at low Ag concentrations favor Th2 responses. The skewed response of the Th2 subset is a cause for allergic diseases. To examine the basis for this opposite stimulatory effects on T helper subsets by DC and B cells, the following specific aims are proposed: (I) to isolate DC from peripheral blood to characterize the factors influencing their survival and proliferating potential; (2) to determine the mechanism for this difference in T helper subset responses in asthma patients and normal individuals; and (3) to determine the T cell epitopes recognized by the two different T helper subsets generated by Ag presentation by DC or B cells. The proposed experiments will provide new insights to the role of DC in asthma and may provide a rational basis for designing immunotherapy for allergic disorders.