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。两个在层粘连蛋白-2中存在不同缺陷的营养不良小鼠品系的特征使我们能够在体内检验这一提议。与正常小鼠相比，层粘连蛋白-2缺陷小鼠(dy/dy)的胸腺大小、胸腺结构和胸腺细胞数量显著减少。对Dy/Dy胸腺中的CD4/CD8群体的检查显示，在糖尿病肾病和SP人群中，相对增加很大，而在DP人群中则显著减少。对糖尿病肾病患者CD44和CD25表达的进一步检测显示，在更成熟的前T细胞人群中，CD44和CD25的表达显著减少。Dy/Dy胸腺的细胞凋亡分析显示，在被膜和被膜下区域，凋亡的DN胸腺细胞显着增加。有趣的是，在表达层粘连蛋白-2突变形式dy2J的营养不良小鼠中，胸腺细胞的发育似乎正常进行，在胎儿和新生dy/dy小鼠中也是如此。我们认为层粘连蛋白-2通过在幼年小鼠发育的特定阶段传递细胞存活和分化信号而在胸腺细胞发育中发挥积极作用。胸腺特异的β1整合素基因敲除小鼠正在准备详细分析β1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.