PLACENTAL PROTEIN 14 AS A UNIQUE IMMUNOREGULATOR

描述：（改编自研究者摘要）本研究的目的 下一个资助期的拨款将用于分析免疫调节 胎盘蛋白14（PP 14）的特性，并设计和 评价具有免疫抑制潜力的PP 14衍生物。这个竞争激烈 续期申请建立在我们实验室在 首次证明PP 14对细胞增殖有直接抑制作用的前一个资助期 T细胞，建立了PP 14独特的“电阻”作用机制， 提高T细胞受体激活阈值，开发了第一个 PP 14的重组衍生物，确定了PP 14的分子结合潜力， 并克隆和表征了动物PP 14同源物。基于我们的小说 了解PP 14的功能特性，我们现在假设PP 14可能 解释怀孕的一些免疫学现象，例如向 孕妇中记录的Th 2细胞因子分泌和临床改善 患有某些自身免疫性疾病有鉴于此，我们打算 研究人员正在向基于PP 14的免疫治疗剂发展，以抑制致病性T细胞。 其具体目标是：1）确定淋巴细胞的表型和命运 2）阐明PP 14介导T细胞凋亡的分子机制 细胞抑制，目的是鉴定关键的膜受体， 受PP 14影响的胞内细胞信号传导途径;和3）设计 具有增强功能的PP 14的重组衍生物，并探索其 在自身免疫和同种免疫动物疾病模型中的治疗用途。的 所提出的研究结合了联合收割机的基本特征和应用特征。

DESCRIPTION: (Adapted from the investigator's abstract) The objectives of this grant in the next funding period will be to analyze the immunoregulatory properties of placental protein 14 (PP14) in greater depth and to design and evaluate PP14 derivatives with immunotherapeutic potential. This competitive renewal application builds upon a body of work from our laboratory during the prior funding period that first demonstrated a direct PP14 inhibitory effect on T cells, established PP14's unique "rheostatic" mechanism of action in elevating T cell receptor activation thresholds, developed the first recombinant derivatives of PP14, defined PP14's molecular binding potentials, and cloned and characterized animal PP14 homologues. Based upon our novel insights into PP14's functional properties, we now hypothesize that PP14 may explain some immunological phenomoena of pregnancy, such as the shift towards Th2 cytokine output and the clinical improvement documented in pregnant women suffering from certain autoimmune diseases. With this in mind, we intend to move towards PP14-based immunotherapeutics for inhibiting pathogenic T cells. The specific aims are: 1) to define the phenotype and fate of lymphocytes inhibited by PP14; 2) to elucidate the molecular mechanisms of PP14-mediated T cell inhibition, with the goal of identifying critical membrane receptor(s) and intracellular cell signaling pathway(s) influenced by PP14; and 3) to design recombinant derivatives of PP14 with enhanced functions, and to explore their therapeutic use in autoimmune and alloimmune animal disease models. The proposed studies combine basic and applied features.