Characterization Of Cell Surface Molecules

我们提出了细胞外基质成分层粘连蛋白-2及其整合素受体VLA-6在胸腺细胞发育中的作用。两种具有不同层粘连蛋白-2缺陷的营养不良小鼠品系的特征使我们能够在体内检查这一建议。与正常窝鼠相比，缺乏层粘连蛋白-2（每天）的小鼠胸腺大小、胸腺结构和胸腺细胞数量显著减少。dy/dy胸腺CD4/CD8群体的检测显示，DN和SP群体相对增加，DP群体显著减少。进一步检测DN群体的CD44和CD25表达，发现在更成熟的前t细胞群体中显著降低。dy/dy胸腺细胞凋亡分析显示，被囊区和被囊下区DN胸腺细胞凋亡显著增加。有趣的是，在表达层粘连蛋白-2 （dy2J）突变形式的营养不良小鼠以及胎儿和新生儿dy/dy小鼠中，胸腺细胞的发育似乎正常进行。我们认为，在年轻成年小鼠的特定发育阶段，层粘胶蛋白-2通过传递细胞存活和分化信号，在胸腺细胞发育中发挥积极作用。胸腺特异性β 1整合素敲除小鼠正准备详细分析β 1整合素在T细胞反应发展中的作用。

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.