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: 6100354
• 负责人: NORA SINGER
• 金额: --
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6100354
• 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.

CD 6是主要由T淋巴细胞表达的细胞表面蛋白。 在胸腺细胞成熟期间发生的CD 6表达增加，和 T淋巴细胞活化后，表明CD 6在 这些过程。探讨CD 6的功能是本课题的重点 提议 T细胞共刺激分子CD 2在胸腺细胞中的作用 胸腺细胞的刺激诱导了CD 6的选择和增加 这就提出了一种可能性，即CD 2诱导的生存信号可能 由CD 6介导。虽然CD 6还没有被证明是重要的， 在胸腺选择过程中，CD 6配体CD 166在胸腺细胞上表达， 慢性淋巴细胞白血病B细胞中CD 6的刺激 确实减少了细胞凋亡提出实验研究 通过CD 2对CD 6表达和磷酸化的发育调节，以及 以确定CD 2诱导的CD 6表达增加是否增强胸腺细胞 生存 CD 6在活化的T淋巴细胞和自身反应性T淋巴细胞中也增加。 克隆的T淋巴细胞。数据显示抗-CD 6单克隆抗体UMCD 6 在体外抑制这些克隆的自身反应性反应表明， 可以在自身免疫过程中作为体内共刺激分子。生存 据报道，自身反应性T淋巴细胞的存在有助于 自身免疫在人类SLE中的作用，但CD 6在人类SLE中的作用，尚未被证实。 示出了研究以确定CD 6调节的改变和 CD 6磷酸化发生在SLE T细胞，为了评估CD 6在SLE T细胞中的作用， 在本申请中提出了SLE T细胞的共活化。 我们假设T淋巴细胞共刺激的功能， 分子CD 6在胸腺细胞发育期间增强T细胞存活， 并向成熟T淋巴细胞传递激活信号。测试 CD 6在胸腺选择过程中的作用，以及成熟T细胞中的n活化 来自SLE患者和正常对照的淋巴细胞，预期增强 我们对CD 6在人类自身免疫性疾病中的作用的理解。