MODULATION OF T CELL DEVELOPMENT AND EFFECTOR FUNCTION

T 细胞发育和效应器功能的调节

• 批准号: 6078393
• 负责人: RANJAN SEN
• 金额: $ 3.15万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078393
• 关键词: DNA binding protein; T cell receptor; T lymphocyte; cell differentiation; cell type; gene expression; genetic recombination; genetically modified animals; histogenesis; laboratory mouse; leukocyte activation /transformation; pentoxifylline; transcription factor

Immature, double negative thymocytes commit themselves for maturation to the double positive phenotype by recombining the PCR beta chain locus and inducing the expression of TCR beta protein. PF inhibits the differentiation of double negative cells into double positive thymocytes. In specific aim 1, the investigator will first identify the stage of the double negative cells and the status of the T cell receptor beta chain locus after the treatment of the cell by PF. If the recombination of the beta chain locus is absent or reduced, the investigator will consider the control of the recombination and transcription of TCR beta locus as a critical event that is affected by the drug PF. If the recombination of the beta chain locus is absent or reduced, the investigator will consider this event as the target for the action of PF. He will then attempt to identify the transcription factors that are required for recombination of the beta chain locus and whose expression/activity is inhibited by PF. If the TCR beta chain locus recombination is unaffected, the investigator will use an appropriate transgenic mouse strain that expresses an already arranged beta chain gene in an attempt to identify the PF mediated molecular block in the development of double positive thymocytes. In the second specific aim, the investigators will examine the expression of Rel transcription factor family members after the treatment of the antigen specific T cell clone with cognate antigen and PF. They will examine the expression and the DNA binding activities of these proteins to determine whether or not the expression or the activity of these proteins is affected by PF.

未成熟的双阴性胸腺细胞致力于成熟 通过重组 PCR β 链基因座实现双阳性表型 并诱导TCRβ蛋白的表达。 PF 抑制 双阴性细胞分化为双阳性细胞 胸腺细胞。 在具体目标 1 中，研究者将首先确定 双阴性细胞的阶段和T细胞受体的状态 PF处理细胞后的β链基因座。 如果 β链位点的重组不存在或减少， 研究者将考虑重组的控制和 TCR beta 位点的转录是一个关键事件，受以下因素影响 药物PF。 如果 β 链基因座重组不存在或 减少，调查员将考虑此事件作为目标 PF 的作用。 然后他将尝试识别转录 β链基因座重组所需的因素和 其表达/活性被PF抑制。 如果 TCR β 链 位点重组不受影响，研究者将使用 表达已安排的适当的转基因小鼠品系 β链基因试图鉴定PF介导的分子 阻断双阳性胸腺细胞的发育。 在第二个 针对特定目标，研究人员将检查 Rel 的表达 抗原处理后的转录因子家族成员 具有同源抗原和 PF 的特异性 T 细胞克隆。 他们将检查 这些蛋白质的表达和 DNA 结合活性 确定这些的表达或活性是否 蛋白质受 PF 影响。