ZAP70 IN T CELL DEVELOPMENT

T 细胞发育中的 ZAP70

• 批准号: 6350237
• 负责人: ANDREW C CHAN
• 金额: $ 19.47万
• 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/6350237
• 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.

性状（改编自研究者摘要）：蛋白酪氨酸 蛋白激酶（PTK）在T细胞的发育中起着不可或缺的作用。 许多细胞质PTK的突变或缺失导致多种细胞质PTK的产生。 免疫缺陷 一种这样的PTK是ζ-链相关的PTK，ZAP-70。 对人类和小鼠的研究证明了ZAP-70的核心重要性 在T细胞发育和T细胞发育功能中。 不存在人 ZAP-70与一种常染色体隐性形式的严重联合 免疫缺陷。 这些患者不产生CD 8+外周T细胞， 无功能性CD 4 + T细胞数量正常。 缺乏ZAP-70的小鼠 基因缺乏CD 4+和CD 8+外周T细胞。 此外，ZAP-70也是 需要适当的选择和发展的T细胞。 而 这些初步研究表明，ZAP-70在 胸腺细胞发育和TCR库的适当选择， ZAP-70可以介导这些广泛多样的生物学机制 答复仍不清楚。 了解ZAP-70如何在 胸腺细胞发育将为免疫细胞中PTKs提供范例 发展，并可能提供对发展差异的见解， 需要CD 4+和CD 8 + T细胞。 此外，这些研究可能提供 药物治疗干预的额外机制信息 设计用于T细胞淋巴瘤、免疫缺陷、自身免疫性疾病和 移植排斥反应