MODIFICATION OF REGULATORY T-LYMPHOCYTE FUNCTION

T淋巴细胞在B细胞调节中起主要作用。 分化 这些免疫调节功能受到以下因素的影响： 不同的T细胞亚群 腺苷能迅速调节 人T淋巴细胞的免疫调节功能，并改变表达 表面抗原和受体。 腺苷可诱导 T辅助/诱导细胞亚群内的抑制活性。“这 研究项目将调查细胞机制和 改变的表面抗原和受体表达的机制， 腺苷诱导的免疫抑制的生化机制。 腺苷反应细胞的身份，其作用时间， 将研究细胞靶向。 部分T淋巴细胞亚群 和腺苷应答性T细胞杂交瘤。 的机制 腺苷诱导的表面标志物改变将使用 选择性放射性标记技术标记表面膜， 膜内和胞质蛋白。 物理上的改变 这些结构的特征和膜分布由 将使用免疫沉淀法研究腺苷， 双向电泳分析。 腺苷被发现 增加磷脂甲基化和花生四烯酸释放。 的作用 磷脂和花生四烯酸代谢的研究将通过 识别T淋巴细胞中磷脂代谢的改变， 腺苷。 磷脂的免疫抑制活性将 研究了 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后的代谢， 确定哪些途径在这个过程中可能是重要的。 腺苷从缺氧和缺血组织以及从 聚集血小板。在这方面，腺苷可能代表一种组织， 受伤信号 抑制性细胞的诱导损害抗体 自体损伤组织的合成可能是重要的 免疫稳态机制限制自身抗体产生。 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，这个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。 （LB）

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)