GAMMA GLUTAMYL TRANSPEPTIDASE & LYMPHOCYTE ACTIVATION

描述：（改编自申请人的摘要）-T 细胞与抗原（Ag）的结合导致效应细胞和记忆细胞的产生。 记忆细胞具有特征性的细胞表面标志物分布，并且能够 对回忆抗原迅速作出反应。CD 4+记忆细胞聚集在 在老化过程中，慢性刺激后，以及自身免疫性 类风湿性关节炎（RA）最近，申请人发现， 胞外酶γ-谷氨酰转肽酶（GGT）在T细胞上被上调 激活，并由记忆T细胞高度表达。高水平的GGT 也发现在T细胞的能力，通过内皮屏障， RA患者外周血T细胞的变化。这种酶在 淋巴细胞生物学尚不清楚，但它可能是重要的维持， 细胞内氧化还原电位和信号事件。其目的是 应用是1）确定GGT是否是记忆T的更好标记物 细胞比以前描述的表面抗原; 2）确定GGT在T细胞中的作用 细胞生物学;和3）确定GGT在细胞跨内皮迁移中的作用， 外周血T细胞建议的实验包括流式细胞术 分析，表达GGT的细胞的功能反应，以确定这些细胞是否 细胞确实有记忆功能;并使用各种策略来破坏 酶活性，申请人将测试GGT对活化的影响， 生长和凋亡。这些实验将提供一个全面的描述， GGT在淋巴细胞中的功能，并应有助于扩大我们的知识 关于记忆T细胞的部分GGT也可能是一个潜在的靶点， 未来的免疫治疗策略

DESCRIPTION: (Adapted from the applicant's abstract) - The interaction of T cells with antigen (Ag) leads to the generation of effector and memory cells. Memory cells have characteristic cell surface marker profiles, and are able to rapidly respond to recall antigens. CD4+ memory cells accumulate in the periphery during aging, following chronic stimulation, and in autoimmune diseases like rheumatoid arthritis (RA). Recently, the applicant has found that the ecto-enzyme gamma glutamyl transpeptidase (GGT) is up-regulated upon T cell activation, and is highly expressed by memory T cells. High levels of GGT are also found in T cells with the capacity to cross endothelial barriers, and on resting peripheral T cells in patients with RA. The role of this enzyme in lymphocyte biology is unclear, but it may be important in maintenance of intracellular re-dox potential and signaling events. The aims of this application are to 1) determine whether GGT is a better marker of memory T cells than previously described surface Ags; 2) determine the role of GGT in T cell biology; and 3) determine the role of GGT in transendothelial migration of peripheral blood T cells. Experiments proposed include flow cytometric analysis, functional responses of GGT expressing cells to determine if these cells indeed have memory function; and using various strategies to disrupt enzymatic activity, the applicant will test the effect of GGT on activation, growth, and apoptosis. These experiments will provide a thorough description of GGT function in lymphocytes, and should be useful in expanding our knowledge about the memory T cell compartment. GGT also may be a potential target in future immunotherapy strategies.