Characterization Of Cell Surface Molecules Important For

细胞表面分子的表征对于重要

• 批准号: 6669390
• 负责人: JOHN COLIGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6669390
• 关键词: T cell receptor; T lymphocyte; cell differentiation; extracellular matrix; gene targeting; genetically modified animals; immunocytochemistry; integrins; laboratory mouse; laminin; protein structure function; thymus; tissue /cell culture

We proposed a role for the extracellular matrix component, laminin-2, and its integrin receptor, VLA-6 in thymocyte development. The characterization of two dystrophic mouse strains with different defects in laminin-2 allowed us to examine this proposal in vivo. Mice deficient in laminin-2, dy/dy, show a significant reduction in thymus size ,alterations in thymic architecture,and number of thymocytes compared to normal littermates. Examination of the CD4/CD8 populations in dy/dy thymi showed large relative increases in the DN and SP populations and a significant decrease in the DP population. Further examination of the DN population for CD44 and CD25 expression showed a remarkable decrease in the more mature pre-T cell populations. Analysis of apoptosis in dy/dy thymi revealed a significant increase in apoptotic DN thymocytes in the capsule and subcapsular regions. Interestingly, thymocyte development appeared to proceed normally in dystrophic mice expressing a mutant form of laminin-2, dy2J, as well as, in fetal and neonatal dy/dy mice. We propose that laminin-2 plays an active role in thymocyte development by delivering cell survival and differentiation signals at specific stages of development in young adult mice. Thymus specfic beta 1 integrin knockout mice are being prepared to analyze in detail the role of beta 1 integrins in development of T cell responses.

我们提出了细胞外基质成分层粘连蛋白-2及其整联蛋白受体VLA-6在胸腺细胞发育中的作用。在层粘连蛋白2中具有不同缺陷的两种营养不良小鼠菌株的表征使我们能够在体内检查该建议。与正常同窝仔相比，缺乏层粘连蛋白2，Dy/dy缺乏层粘连蛋白2的小鼠显着降低了胸腺大小，胸腺结构的改变以及胸腺细胞的数量。对Dy/Dy Thymi中CD4/CD8种群的检查显示，DN和SP种群的相对增加很大，并且DP群体显着下降。对CD44和CD25表达的DN种群的进一步检查显示出更为成熟的T细胞细胞种群的显着降低。 Dy/dy Thymi中凋亡的分析表明，囊囊和囊皮区域的凋亡DN胸腺细胞显着增加。有趣的是，在表达层粘连蛋白-2，DY2J以及胎儿和新生儿DY/DY/DY小鼠的突变形式的营养不良小鼠中，胸腺细胞发育似乎正常进行。我们建议通过在年轻小鼠发育的特定阶段传递细胞存活和分化信号，在胸腺细胞发育中起积极作用。胸腺特定β1整合素基因敲除小鼠正在准备详细分析β1整合蛋白在T细胞反应发展中的作用。