67KD NON INTEGRIN LAMININ BINDING PROTEIN IN T LYMPHOCYTE MEDIATED SKIN DISEASE

T 淋巴细胞介导的皮肤病中的 67KD 非整合素层粘连蛋白结合蛋白

• 批准号: 6100661
• 负责人: Stephen M Canfield
• 金额: $ 7.6万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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/6100661
• 关键词: T lymphocyte; binding proteins; cell line; cell migration; immunologic memory; inflammation; laminin; skin disorder

T cell interactions with laminin, the major glycoprotein of the basement membrane, are important in lymphocyte migration in the cutaneous inflammatory response (1-4). However, the interactions of lymphocytes with laminin are only beginning to be understood. Underlying the proposed studies is our finding that the 67 kD laminin binding protein (p67 LBP) is expressed on the surface of activated but not resting T lymphocytes. We initially identified p67 LBP by the differential expression of the mRNA encoding its polypeptide precursor, p37 LBPP, in a pair of T cell tumor line subclones that represent phenotypic characteristics of either resting or activated T cells. Subsequently, suing the anti-p67 LBP monoclonal antibody (mAb) MLuC5(6), we demonstrated that p67 LBP is expressed on activated memory T cells, and not expressed on naive or resting cells. The present grant addresses the T cell requirements for p67 LBP expression, the nature of the subset of T lymphocytes which express p67 LBP, and the role that p67 LBP plays in T cell migration into the skin. The long term objective of these studies is to define the role of p67 LBP in cutaneous T cell homing, and to identify potential therapeutic targets in the treatment of immune- mediated skin disease. We propose to address the following specific aims: 1. What stimuli induce the expression of p67 LBP on normal T cell? 2. What is the phenotype of the p67 LBP-expressing T cell subset with respect to the T lymphocytes known to traffic to the skin? 3. Do the T cells infiltrating cutaneous sites of inflammation express p67 LBP?

T细胞与基底膜主要糖蛋白层粘连蛋白的相互作用 膜，对淋巴细胞在皮肤中的迁移很重要 炎症反应(1-4)。然而，淋巴细胞之间的相互作用 对层粘连蛋白的研究才刚刚开始。潜在的 提出的研究是我们发现67kD的层粘连蛋白结合蛋白 (P67 LBP)表达在激活的T细胞表面，而不是静止的T细胞表面 淋巴细胞。我们最初通过差值确定了p67 LBP 编码其多肽前体p37 LBPP的mRNA在 一对代表表型的T细胞肿瘤亚克隆 静息或激活的T细胞的特征。后来， 应用抗p67 LBP单抗MLuC5(6)，我们 证实p67 LBP在激活的记忆T细胞上表达，并且 不表达在幼稚细胞或静息细胞上。目前的赠款针对的是 T细胞对p67 LBP表达的要求，其子集的性质 表达p67 LBP的T淋巴细胞以及p67 LBP在 T细胞迁移到皮肤中。这些研究的长期目标是 确定p67 LBP在皮肤T细胞归巢中的作用，并 寻找治疗免疫性疾病的潜在靶点 介导的皮肤病。我们建议解决以下具体问题 目标： 1.哪些刺激可诱导正常T细胞p67 LBP的表达？ 2.表达p67 LBP的T细胞亚群的表型 尊重已知的运输到皮肤的T淋巴细胞？ 3.浸润性皮肤炎症部位的T细胞表达 P67 LBP？