MODIFICATION OF REGULATORY T-LYMPHOCYTE FUNCTION

T淋巴细胞在B细胞的调节中起主要作用 差异化。这些免疫调节功能是由 不同的T细胞亚群。腺苷可以迅速调节 人T淋巴细胞的免疫调节功能及其表达的改变 表面抗原和受体。腺苷诱导骨质疏松症发生 “辅助性T细胞/诱导性T细胞”子集内的抑制活性。这 研究项目将研究细胞机制和 表面抗原和受体表达改变的机制及其机制 腺苷诱导免疫抑制的生化机制。 腺苷反应细胞的特性，其作用时间，以及 手机目标将被调查。分离的T淋巴细胞亚群 将使用腺苷反应性T细胞杂交瘤。其作用机制 对于腺苷诱导的表面标记改变，将使用 用于标记表面膜的选择性放射性标记技术， 膜内蛋白和胞质蛋白。身体上的变化 这些结构的特征和膜分布 腺苷将使用免疫沉淀进行研究，然后 采用双向电泳法进行分析。腺苷被发现可以 增加磷脂甲基化和花生四烯酸的释放。角色 磷脂和花生四烯酸代谢的研究将由 识别T淋巴细胞磷脂代谢的改变 通过腺苷。磷脂的免疫抑制活性将是 调查过了。花生四烯酸选择性抑制剂的作用 将研究腺苷诱导的免疫抑制的代谢 确定哪些途径在这一过程中可能很重要。 腺苷从缺氧和缺血组织中释放，也从 聚集血小板。在这一点上，腺苷可以代表一种组织 受伤信号。诱导抑制细胞破坏抗体 对自体损伤组织的合成可能是一个重要的 限制自身抗体产生的免疫平衡机制。自.以来 腺苷快速修饰T淋巴细胞环核苷酸、磷脂、 和花生四烯酸代谢，这一系统提供了一个机会 研究这些事件之间的关系，并应提供见解 免疫调节的生化基础。(磅)

T-lymphocytes play a major role in the regulation of B-cell differentiation. These immunoregulatory functions are effected by distinct T-cell subsets. Adenosine can rapidly modulate the immunoregulatory function of human T-lymphocytes and alter the expression of surface antigens and receptors. Adenosine induces development of suppressor activity within a subset of "T-helper/inducer cells." This research project will investigate the cellular mechanisms and the mechanisms of altered surface antigen and receptor expression and the biochemical mechanisms operative in adenosine-induced immunosuppression. The identity of the adenosine responsive cell, its time of action, and cellular target will be investigated. Fractionated T-lymphocyte subsets and adenosine responsive T-cell hybridomas will be used. The mechanisms of adenosine-induced, surface marker alteration will be investigated using selective radioactive labeling techniques to tag surface membrane, intramembrane, and cytosolic proteins. Alterations in the physical characteristics and membrane distribution of these structures caused by adenosine will be investigated using immunoprecipitation followed by analysis with two-dimensional electrophoresis. Adenosine was found to increase phospholipid methylation and arachidonic acid release. The role of phospholipid and arachidonic acid metabolism will be investigated by identifying alterations in phospholipid metabolism in T-lymphocytes caused by adenosine. The immunosuppressive activity of phospholipids will be investigated. The effects of selective inhibitors of arachidonic acid metabolism upon adenosine-induced immunosuppression will be studied to determine which pathways may be important in this process. Adenosine is released from hypoxic and ischemic tissues as well as from aggregating platelets. In\this regard, adenosine may represent a tissue injury signal. The induction of suppressor cells which impair antibody synthesis to autologous injured tissues may be an important immunohomeostatic mechanism to limit autoantibody production. Since adenosine rapidly modifies T-lymphocyte cyclic nucleotide, phospholipid, and arachidonic acid metabolism, this system provides an opportunity to study the relationship between these events and should provide insights into the biochemical basis of immunoregulation. (LB)