Requirements for regulatory T cell development

描述(申请人提供)：自然调节性T细胞(CD25+， CD45RBlo)似乎负责控制自身反应性T细胞 活动，因此，自身免疫性疾病的发展。他们是 存在于幼鼠体内，并表达一种激活/记忆表面标记 表型。这些细胞不会对各种刺激做出反应而增殖， 但在体外对效应性T细胞的增殖有很强的抑制作用。 虽然在了解它们的作用机制方面已经取得了一些进展 行动，对他们的发展或外围设备的需求知之甚少 激活。有证据表明，自然调节性T细胞可能会经历 在胸腺和外周部位的选择/激活，例如 粘膜。尤其是肠道，是这个粘膜部位的有力候选者。 因为通过这些组织暴露于抗原往往会导致耐受性 而不是免疫力，而且抗原量巨大且极其多样化。我们 提出自然调节性T细胞发育需要两个阶段 激活以成为完全功能；诱导和效应器阶段， 这两种疾病都可能累及肠道粘膜。使用体外和体内试验， 我们的研究将涉及三个具体目标：(1)表征基本的 自然调节性T细胞发育的要求；(2)确定 GALT是否参与自然调节性T细胞的诱导阶段 发展；以及(3)确定高尔特对第二阶段是否至关重要 外周自然调节性T细胞的激活。这些实验 可以确定调节性T细胞发育的要求，从而， 确定可以通过治疗性操作来预防和/或 治疗自身免疫性疾病。

DESCRIPTION (provided by applicant): Natural regulatory T cells (CD25+, CD45RBlo) appear to be responsible for controlling autoreactive T cell activity and, thereby, the development of autoimmune diseases. They are present in naive mice and express an activation/memory surface marker phenotype. These cells do not proliferate in response to a variety of stimuli, but are very potent inhibitors of effector T cell proliferation in vitro. Although some progress has been made in understanding their mechanisms of action, little is known about their requirements for development or peripheral activation. Evidence suggests that natural regulatory T cells may undergo selection/activation at both the thymus and peripheral sites, such as the mucosa. The gut, in particular, is a strong candidate for this mucosal site since exposure to antigen through these tissues tends to result in tolerance rather than immunity, and the antigenic load is huge and extremely diverse. We propose that natural regulatory T cell development requires two stages of activation to become fully functional; an induction and an effector stage, both of which may involve the gut mucosa. Using in vitro and in vivo assays, our studies will address three specific aims: (1) to characterize the basic requirements for development of natural regulatory T cells; (2) to determine whether GALT is involved in the induction stage of natural regulatory T cell development; and (3) to determine whether GALT is critical for the secondary activation of natural regulatory T cells in the periphery. These experiments may determine the requirements for regulatory T cell development, and thereby, identify pathways that can be therapeutically manipulated to prevent and/or treat autoimmune diseases.