CHARACTERIZATION OF CELL SURFACE MOLECULES IMPORTANT FOR IMMUNE FUNCTION

在以前的体外研究中，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。 层粘连蛋白-2中具有不同缺陷的两种营养不良小鼠品系的表征使我们能够在体内检查这一提议。 层粘连蛋白-2缺乏的小鼠（dy/dy）与正常同窝仔相比，胸腺大小和胸腺细胞数量显著减少。 这些小鼠还表现出胸腺结构的明显改变。 对dy/dy胸腺中的CD 4/CD 8群体的检查显示DN（CD 4-CD 8-）和SP（CD 4 + CD 8-，CD 4-CD 8+）群体的相对较大增加以及DP（CD 4 + CD 8+）群体的显著减少。 进一步检查DN群体的CD 44和CD 25表达显示，更成熟的前T细胞群体显著减少。原位细胞凋亡分析，并通过流式细胞术，在dy/dy胸腺显示了显着增加，在被囊和被囊下区域的凋亡DN胸腺细胞。 有趣的是，胸腺细胞的发育似乎正常进行，在营养不良的小鼠表达层粘连蛋白-2，dy 2 J的突变形式，以及在胎儿和新生儿的dy/dy小鼠。 我们认为，层粘连蛋白2在胸腺细胞发育中起着积极的作用，在特定的发展阶段，在年轻的成年小鼠提供细胞的生存和分化信号。

In previous in vitro studies, 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 and number of thymocytes compared to normal littermates. These mice also exhibited apparent alterations of thymic architecture. Examination of the CD4/CD8 populations in dy/dy thymi showed large relative increases in the DN (CD4-CD8-) and SP (CD4+CD8-, CD4-CD8+) populations and a significant decrease in the DP (CD4+CD8+) 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 situ, and by flow cytometry, 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.