CD6 T LYMPHOCYTE COSTIMULATORY MOLECULE--IMMUNE DEVELOPMENT & AUTOIMMUNE DISEASE

CD6 T 淋巴细胞共刺激分子--免疫发育

• 批准号: 6201487
• 负责人: NORA SINGER
• 金额: $ 21.8万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201487
• 关键词: CD antigens; CD2 molecule; T lymphocyte; autoimmune disorder; clinical research; developmental immunology; human subject; leukocyte activation /transformation; lymphocyte proliferation; systemic lupus erythematosus

CD6 is a cell surface protein expressed primarily by T-lymphocytes The increase in CD6 expression that occurs during thymocyte maturation, and following T-lymphocyte activation, indicates an important role for CD6 in these processes. Exploring the function of CD6 is the focus of this proposal. The T cell co-stimulatory molecule CD2 is important in thymocyte selection, and increase in CD6 are induced by stimulation of thymocyte CD2; this raises the possibility that the CD2 induced survival-signal may be mediated by CD6. Although CD6 has not yet been shown to be important during thymic selection, the CD6 ligand, CD166 is expressed on thymic epithelium, and stimulation of CD6 in chronic lymphocytic leukemia B-cells does decrease apoptotic death. Experiments are proposed to study developmental regulation of CD6 expression and phosphorylation by CD2, and to determine if CD2-induced increased in CD6 expression enhance thymocyte survival. CD6 is also increased in activated T lymphocytes, and in autoreactive cloned T lymphocytes. Data showing that anti-CD6 monoclonal antibody UMCD6 inhibits autoreactive responses of such clones in vitro suggests that CD6 may act as a co-stimulatory molecule in vivo during autoimmunity. Survival of autoreactive T lymphocytes has been reported to contribute to autoimmunity in human SLE but a role for CD6 in hum SLE, has not yet been shown. Studies to determine if alterations in the regulation of CD6 and CD6 phosphorylation occur in SLE T cells, and to assess the role of CD6 in co-activation of SLE T cells are proposed in this application. We hypothesize that the function of the T lymphocyte co-stimulatory molecule CD6 is to enhance T-cell survival during thymocyte development, and to transduce activating signals to mature T lymphocyte. Testing the role of CD6 during thymic selection, and n activation in mature T lymphocyte from SLE patients and normal controls, is expected to enhance our understanding of the role of CD6 in human autoimmune disease.

CD6是一种细胞表面蛋白，主要由T淋巴细胞表达 在胸腺细胞成熟过程中CD6表达增加，以及 在T淋巴细胞活化之后，表明CD6在 这些过程。探讨CD6的功能是本研究的重点。 求婚。 T细胞共刺激分子CD2在胸腺细胞中起重要作用 CD6的选择和增加是由胸腺细胞刺激诱导的 CD2；这增加了CD2诱导的生存信号可能 由CD6介导。尽管CD6尚未被证明是重要的 在胸腺选择过程中，CD6配体CD166在胸腺上表达 慢性淋巴细胞白血病B细胞上皮细胞及CD6的刺激作用 确实减少了细胞凋亡性死亡。建议通过实验来研究 CD2对CD6表达和磷酸化的发育调控，以及 检测CD2诱导的CD6表达增加是否增强胸腺细胞 生死存亡。 CD6在活化的T淋巴细胞和自身反应性T细胞中也增加 克隆的T淋巴细胞。资料显示，抗CD6单抗UMCD6 在体外抑制这类克隆的自身反应表明CD6 在自身免疫过程中可能作为体内的共刺激分子。生死存亡 据报道，自身反应性T淋巴细胞参与了 人类系统性红斑狼疮自身免疫但CD6在人类系统性红斑狼疮中的作用 展示了。研究以确定CD6和CD6调节的变化是否 CD6在SLE T细胞中发生磷酸化，并评估CD6在SLE T细胞中的作用 在这一应用中，提出了SLE T细胞的共激活。 我们假设T淋巴细胞的共刺激功能 CD6分子是为了在胸腺细胞发育过程中提高T细胞的存活率， 并将激活信号传递给成熟的T淋巴细胞。测试 CD6在胸腺选择中的作用及成熟T细胞中N的激活 来自SLE患者和正常对照组的淋巴细胞有望增强 我们对CD6在人类自身免疫性疾病中的作用的理解。