Requirements for regulatory T cell development

描述（由申请人提供）： 天然调节性T细胞（CD 25+， CD 45 RBlo）似乎负责控制自身反应性T细胞 活动，从而导致自身免疫性疾病的发展。他们是 存在于幼稚小鼠中并表达激活/记忆表面标记物 表型这些细胞不会对各种刺激作出反应而增殖， 但在体外是效应T细胞增殖的非常有效的抑制剂。 尽管在了解其机制方面取得了一些进展， 行动，很少有人知道他们的要求，发展或周边 activation.有证据表明，天然调节性T细胞可能经历 在胸腺和外周部位的选择/激活，如 粘膜特别是肠道，是该粘膜部位的强有力候选者 因为通过这些组织暴露于抗原往往导致耐受性 而不是免疫力，抗原量是巨大的，而且非常多样化。我们 提出自然调节性T细胞的发育需要两个阶段， 激活以变得完全功能化;诱导和效应阶段， 两者都可能涉及肠粘膜。使用体外和体内测定， 我们的研究将涉及三个具体目标：（1）描述基本的 天然调节性T细胞的发育要求;（2）确定 GALT是否参与天然调节性T细胞的诱导阶段 （3）确定GALT是否是次要的 激活外周中的天然调节性T细胞。 这些实验 可以决定调节性T细胞发育的要求，从而， 确定可以治疗性地操纵以预防和/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.