ZAP70 IN T CELL DEVELOPMENT

T 细胞发育中的 ZAP70

• 批准号: 2871966
• 负责人: ANDREW C CHAN
• 金额: $ 17.81万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-17 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2871966
• 关键词: T cell receptor; T lymphocyte; biological signal transduction; cell differentiation; gene mutation; genetic transcription; laboratory mouse; phosphorylation; protein tyrosine kinase

DESCRIPTION (Adapted from Investigator's abstract): Protein tyrosine kinases (PTKs) play an integral role in the development of T cells. Mutations or the absence of a number of cytoplasmic PTKs result a variety of immunodeficiencies. One such PTK is the zeta-chain associated PTK, ZAP-70. Studies in both humans and mice demonstrate the central importance of ZAP-70 in T cell development and T cell development function. Absence of human ZAP-70 is associated with an autosomal recessive form of severe combined immunodeficiency. These patients develop no CD8+ peripheral T cells and have normal numbers of nonfunctional CD4+ T cells. Mice lacking the ZAP-70 gene lack both CD4+ and CD8+ peripheral T cells. Moreover, zap-70 is also required for the appropriate selection and development of T cells. While these initial studies demonstrate the central importance of ZAP-70 in thymocyte development and appropriate selection of the TCR repertoire, the mechanism(s) by which ZAP-70 can mediate these vastly diverse biological responses remain unclear. An understanding of how ZAP-70 functions in thymocyte development will provide a paradigm for PTKs in immune cell development and may provide insights into differences in the developmental requirements of CD4+ and CD8+ T cells. Moreover, these studies may provide additional mechanistic information for therapeutic interventions in drug design for T cell lymphomas, immunodeficiencies, autoimmune diseases, and transplantation rejection.

描述(摘自《调查者摘要》)：蛋白质酪氨酸 蛋白酪氨酸激酶(PTK)在T细胞的发育中起着不可或缺的作用。 许多细胞质PTK的突变或缺失会导致多种 免疫缺陷。一种这样的PTK是Zeta链相关的PTK，ZAP-70。 在人类和小鼠身上的研究证明了ZAP-70的核心重要性 在T细胞发育和T细胞发育中的作用。人类的缺席 ZAP-70与一种常染色体隐性形式的重症联合 免疫缺陷。这些患者没有CD8+外周T细胞， 有正常数量的无功能的CD4+T细胞。缺乏ZAP-70的小鼠 该基因缺乏CD4+和CD8+外周T细胞。此外，ZAP-70也是 对于T细胞的适当选择和发育是必需的。而当 这些初步研究证明了ZAP-70在 胸腺细胞的发育和TCR谱系的适当选择 ZAP-70介导这些差异巨大的生物的机制(S) 对此的回应仍不清楚。对ZAP-70在心脏疾病中的作用 胸腺细胞的发育将为免疫细胞中的PTKs提供一个范例 发展，并可能提供对发展的差异的洞察力 对CD4+和CD8+T细胞的需求。此外，这些研究可能会提供 药物治疗干预的额外机制信息 为T细胞淋巴瘤、免疫缺陷、自身免疫性疾病和 移植排斥反应。