IN VITRO INDUCTION OF SUPPRESSOR T CELLS

抑制性 T 细胞的体外诱导

• 批准号: 3445806
• 负责人: PERRIE B HAUSMAN
• 金额: $ 3.8万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1986-08-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3445806
• 关键词: B lymphocyte; T lymphocyte; cell cell interaction; cell differentiation; immunoregulation; interleukin 2; leukocyte activation /transformation; lymphokines; macrophage; radioimmunoassay; suppressor T lymphocyte; tissue /cell culture

It is the aim of this research proposal to dissect the requirements for the in vitro generation of suppressor T cells (Ts). As suppressor cells have been implicated in the normal maintenance of immune system homeostasis, a better understanding of the complex requirements needed to generate these important regulatory cell populations will hopefully enable us to better comprehend and rectify Ts defects in autoimmune diseases, immunodeficiency disorders, and cancer. To this end we have developed an in vitro system for the generation of 2nd order (Ts2) and effector suppressor cells (Ts3) specific for the 4-hydroxy-3-nitrophenyl acetyl hapten (NP). Cyclophosphamide treated responder populations, which are functionally depleted of both Ts2 and Ts3 cells, are challenged in vitro with the T dependent antigen NP-horse red blood cells (NP-HRBC) for 5 days. On the 4th day of culture, separate subcultures containing experimental Ts2 and Ts3 populations are added to responder cultures. One day later, the direct anti-NP specific plaque forming cell (PFC) responses are determined. This methodology will allow us to directly identify and fully characterize both precursor and mature Ts populations, the role of accessory cells, soluble mediators, and the genetic restrictions which control the differentiation and expression of Ts activity. Phenotypic analysis of both mature and precursor Ts populations with a panel of monoclonal reagents may allow us to identify markers that are differentially expressed on various Ts subsets and to determine when Ts develop their idiotypic specificities. By analyzing the ability of fetal liver and thymic cell populations to generate Ts2 or Ts3 activity, we will be in a position to determine when suppressor cells become immunocompetent. We will also examine the role of accessory cells in the generation of Ts. We will perform experiments to determine whether MHC homology between the macrophages and T or B cells is required for suppressor cell induction and whether factors from macrophages influence the induction process. In addition the role of B cells in Ts induction would be examined and the general question of the importance of B cell receptors in the development of T cells can be addressed. Finally a better understanding of the requirements for suppressor cell induction may enable us to develop a method for maintaining long-term, untransformed suppressor T cell lines in culture.

这项研究提案的目的是剖析对 体外产生抑制性T细胞(Ts)。因为抑制子细胞 与正常维持免疫系统的动态平衡有关 更好地理解生成以下内容所需的复杂需求 重要的调节细胞群体有望使我们能够更好地 了解和纠正自身免疫性疾病、免疫缺陷的TS缺陷 疾病和癌症。为此，我们开发了一种体外系统 2级(TS2)和效应抑制细胞(TS3)的产生 专用于4-羟基-3-硝基苯乙酰半抗原(NP)。 环磷酰胺治疗的应答者群体，其功能是 TS2和TS3细胞都被耗尽，在体外用T细胞挑战 依赖抗原NP-马红细胞(NP-HRBC)培养5天。论 培养第4天，分离包含实验性TS2和TS2的继代培养 TS3人群被添加到响应者培养中。一天后，直接 测定抗NP特异性斑块形成细胞(PFC)反应。这 方法论将使我们能够直接识别并充分表征这两个 前体和成熟ts群体，辅助细胞的作用，可溶 调节因子和控制分化的遗传限制 和TS活性的表达。成熟期和成熟期的表型分析 带有一组克隆试剂的前体ts群体可能会让我们 识别在不同TS子集上差异表达的标记 并确定T细胞何时形成其独特型特异性。通过 分析胎儿肝脏和胸腺细胞群的能力 生成TS2或TS3活动，我们将能够确定何时 抑制细胞变得具有免疫活性。我们还将研究 辅助细胞在TS的生成中。我们将进行实验，以 确定巨噬细胞与T或B细胞之间的MHC同源性是否 抑制细胞诱导所需以及巨噬细胞中的因子 影响诱导过程。此外，B细胞在TS中的作用 将研究归纳法和B的重要性的一般问题 细胞受体在T细胞发育中的作用可以解决。最后是一个 更好地理解抑制细胞诱导的要求可能 使我们能够开发出一种方法来保持长期的、未改变的 抑制培养中的T细胞系。