Ocampo Jurandy Susana Patricia, de Brito José Marques, Corrêa-de-Santana Eliane, Borojevic Radovan, Villa-Verde Déa Maria Serra, Savino Wilson
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Manguinhos, Rio de Janeiro, Brazil.
Cell Immunol. 2008;254(1):1-9. doi: 10.1016/j.cellimm.2008.06.005. Epub 2008 Jul 21.
Thymocyte differentiation occurs within the thymic microenvironment, consisting of distinct cell types and extracellular matrix (ECM) elements. One of these ECM proteins is laminin. Previous experiments showed that laminin mediates interactions between thymocytes and thymic epithelial cells (TEC) in mice. Since, laminin comprises a family of related isoforms, we searched for laminin isoform expression in the human thymus. We found constitutive gene expression of various laminin chains in TEC preparations, comprising laminin-111 and laminin-211 isoforms. Immunocytochemistry revealed a selective laminin-211 distribution in the thymic lobules. In vitro functional assays revealed that laminin-211 enhances TEC/thymocyte adhesion and thymocyte release from thymic nurse cells, as well as the reconstitution of these complexes. Conversely, these interactions are blocked by monoclonal antibodies specific for laminin-211 and the laminin receptor VLA-6. Our results reinforce the notion that distinct laminin isoforms in the human thymus are relevant for lymphoepithelial interactions.
胸腺细胞分化发生在胸腺微环境中，该微环境由不同的细胞类型和细胞外基质（ECM）成分组成。这些ECM蛋白之一是层粘连蛋白。先前的实验表明，层粘连蛋白介导小鼠胸腺细胞与胸腺上皮细胞（TEC）之间的相互作用。由于层粘连蛋白由一系列相关的异构体组成，我们研究了人胸腺中层粘连蛋白异构体的表达情况。我们发现TEC制剂中各种层粘连蛋白链的组成性基因表达，包括层粘连蛋白-111和层粘连蛋白-211异构体。免疫细胞化学显示层粘连蛋白-211在胸腺小叶中有选择性分布。体外功能试验表明，层粘连蛋白-211可增强TEC/胸腺细胞的粘附以及胸腺细胞从胸腺哺育细胞中的释放，以及这些复合物的重建。相反，这些相互作用被针对层粘连蛋白-211和层粘连蛋白受体VLA-6的单克隆抗体所阻断。我们的结果强化了这样一种观念，即人胸腺中不同的层粘连蛋白异构体与淋巴上皮相互作用相关。
