MODIFICATION OF REGULATORY T-LYMPHOCYTE FUNCTION

这个项目的长期目标是阐明这些机制。 类胡萝卜素(即“局部激素”)是如何调节T淋巴细胞的？ 功能。我们把注意力集中在 腺苷(ADO)的免疫调节特性。阿多被解放了 从低氧细胞和炎症反应的过程中。 我们之前已经表明，人类T细胞的短暂暴露- 淋巴细胞对低浓度的腺苷(1um)引起的快速 T细胞表面抗原表达的选择性改变 (如T4、T8)和受体(Fc)，并诱导 T细胞依赖B细胞分化的抑制细胞。这些 这些事件是由细胞表面腺苷受体介导的。在最近 多年来，在表征方面已经取得了相当大的进展 腺苷受体亚型。我们假设阿杜，通过 特异性腺苷受体，调节细胞表面的表达 结构的功能直接与腺苷的能力有关 改变T淋巴细胞免疫调节行为。去调查 我们提出的这一假设是为了(1)确定腺苷受体 腺苷介导的免疫事件的特异性 受体特异性激动剂和拮抗剂，(2)研究 腺苷受体亚型在T淋巴细胞亚群上的分布 使用腺苷受体特异性单抗以及 特异性激动剂和拮抗剂及其相关腺苷受体 T细胞亚群的分布与其免疫调节功能 (3)鉴定ADO新表达的细胞表面抗原 激活的抑制细胞，并探讨它们在ADO-1中的作用 诱导免疫抑制。这将在开发过程中完成 抗“腺苷激活抗原”(AAA)的单抗。 根据我们的初步观察，ADO激活了 抑制细胞通过限制B细胞的可用性发挥作用 生长和分化因子(BCGF、BCDF)我们将 研究这些影响对BCGF和BCDF的特异性 从各种来源以及其他淋巴因子和检查 AAA在调节BCGF和BCDF代谢中的作用我们 也将(4)确定负责ADO的腺苷受体 诱导的磷脂和花生四烯酸的变化 代谢和(5)进一步鉴定腺苷受体 AAA的特异性、靶细胞及其在AAA中的作用 增强对同种异体细胞的反应。腺苷 免疫调节系统可能是一个重要的生理系统。 并对它们的腺苷受体特异性进行了研究 免疫调节事件可能最终导致更大的能力 使用腺苷调节特定的免疫调节功能 受体特异性激动剂和/或拮抗剂。

The long-term goal of this project is to elucidate the mechanisms by which autacoids (i.e. "local hormones") modulate T-lymphocyte function. We have focused our attention upon the immunoregulatory properties of adenosine (Ado). Ado is liberated from hypoxic cells and in the course of inflammatory reactions. We have previously shown that brief exposure of human T- lymphocytes to low concentrations of Ado (1 uM) causes rapid but selective alteration in the expression of T-cell surface antigens (e.g. T4, T8) and receptors (Fc) and induces the activation of a suppressor cell of T-cell dependent B-cell differentiation. These events are mediated by cell surface Ado receptors. In recent years there has been considerable progress in the characterization of Ado receptor subtypes. We hypothesize that Ado, acting via specific Ado receptors, modulates the expression of cell surface structures whose function relates directly to adenosine's ability to alter T-lymphocyte immunoregulatory behavior. To investigate this hypothesis we propose to (1) determine the Ado receptor specificity of Ado mediated immunologic events using Ado receptor specific agonists and antagonists, (2) study the distribution of Ado receptor subtypes on T-lymphocyte subsets using Ado receptor specific monoclonal antibodies as well as specific agonists and antagonists and correlate Ado receptor distribution on T-cell subsets to their immunoregulatory function and (3) identify cell surface antigens newly expressed on Ado activated suppressor cells and investigate their role in Ado- induced immunosuppression. This will be done be developing monoclonal antibodies to "adenosine activation antigens" (AAA). Based upon our preliminary observations that Ado activated suppressor cells function by limiting the availability of B-cell growth- and differentiation factors (BCGF, BCDF) we will investigate the specificity of these effects on BCGF and BCDF from various sources as well as on other lymphokines and examine the role of AAA in regulating BCGF and BCDF metabolism. We will also (4) identify the Ado receptors responsible for Ado induced alterations in phospholipid and arachidonic acid metabolism and (5) further characterize the Ado receptor specificity, target cells and role of AAA in the phenomenon of Ado enhancement of responses to allogeneic cells. The adenosine immunoregulatory system may be a physiologically important one and study of the Ado receptor specificity of these immunoregulatory events may ultimately lead to greater ability to modulate specific immunoregulatory functions using Ado receptor specific agonists and/or antagonists.