IN VITRO STUDIES OF T-CELL UNRESPONSIVENESS

描述（改编自研究者摘要和/或目的）：主要 部分研究是基于申请人以前的工作 证明Ia+鼠角质形成细胞与同基因的 T细胞克隆导致延长的抗原特异性T细胞耐受。 虽然“异常”辅助细胞产生T细胞的机制 不能完全理解，这显然是由于他们的 不能提供尚未表征的第二信号。 生产 通过在“异常”辅助细胞上呈递抗原的克隆性无能 似乎在小鼠体内也有效。 因此，如果这种方法 T细胞无反应性诱导可以在人类中产生， 对于治疗T细胞介导的 过敏性疾病，如过敏性接触性皮炎。 虽然人类 T细胞耐受性以前曾在人类中产生过， 研究以确定克隆无反应性是否可以在人类T细胞中产生， 细胞 这一点很重要，因为有几种机制（抑制T 细胞、克隆缺失、克隆无反应性），通过该方法可以制备T细胞 反应迟钝 这三个具体目标提出研究免疫生物学 人T细胞克隆性无能，以检查表型和功能 与其诱导相关的T细胞变化，并确定是否 无反应性T细胞在其活化途径中具有异常。 建立这种T细胞无反应性的体内模型， 为试图诱导无反应性提供理论基础 在过敏性疾病患者体内。

DESCRIPTION (adapted from investigator's abstract and/or aims): The major portion of the study is based on the applicant's previous work demonstrating that coincubation of Ia+ murine keratinocytes with syngeneic T cell clones results in prolonged antigen specific T cell tolerance. Although the mechanism by which "aberrant" accessory cells produce T cell anergy is not completely understood, it apparently is due to their inability to provide an as yet uncharacterized second signal. Production of clonal anergy by presentation of antigen on "aberrant" accessory cells appears to be operative in mice in-vivo as well. Thus, if such a method of T cell unresponsiveness induction could be produced in humans, it would have important ramifications for the treatment of T cell mediated hypersensitivity diseases such as allergic contact dermatitis. While human T cell tolerance has been produced in humans before, there have been no studies to determine whether clonal anergy can be produced in human T cells. This is important since there are several mechanisms (suppressor T cell, clonal deletion, clonal anergy) by which T cells can be made unresponsive. The three specific aims propose to study the immunobiology of human T cell clonal anergy, to examine the phenotypic and functional changes in T cells associated with its induction, and to determine whether anergic T cells have abnormalities in their activation pathways. Establishment of such an in-vivo model of T cell unresponsiveness should provide the theoretical basis for attempts to induce unresponsiveness in-vivo in patients with allergic diseases.