GAMMA GLUTAMYL TRANSPEPTIDASE & LYMPHOCYTE ACTIVATION

描述：(改编自申请人的摘要)-T的互动 含有抗原的细胞会导致效应细胞和记忆细胞的产生。 存储单元具有特征的细胞表面标记轮廓，并且能够 对召回抗原做出快速反应。CD4记忆细胞在脑内蓄积 在衰老、慢性刺激后和自身免疫中的外周 类风湿性关节炎(RA)等疾病。最近，申请人发现 胞外酶γ谷氨酰转肽酶(GGT)在T细胞上的上调 激活，并在记忆T细胞中高表达。高水平的GGT是 在具有跨越内皮屏障能力的T细胞中也发现了这种情况，以及其他 类风湿关节炎患者静息外周T细胞的变化这种酶在体内的作用 淋巴细胞生物学尚不清楚，但它可能在维持 细胞内氧化还原电位和信号事件。这样做的目的是 应用1)确定GGT是否是记忆T的更好标记物 细胞表面AGS；2)确定GGT在T细胞中的作用 细胞生物学；3)确定GGT在血管内皮细胞迁移中的作用。 外周血T细胞。建议的实验包括流式细胞术 分析GGT表达细胞的功能反应，以确定这些 细胞确实具有记忆功能，并使用各种策略来破坏 酶活性，申请者将测试GGT对激活的影响， 生长和细胞凋亡。这些实验将全面描述 GGT在淋巴细胞中的功能，应该有助于扩大我们的知识 关于记忆T细胞室。GGT也可能成为 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.