Ruiz P, Wiles M V, Imhof B A
Basel Institute for Immunology, Switzerland.
Eur J Immunol. 1995 Jul;25(7):2034-41. doi: 10.1002/eji.1830250735.
During embryogenesis, colonization of the thymic rudiment by hemopoietic progenitor cells depends on the adhesion of these cells to the jugular endothelium. Previously, we showed that progenitor T cells (pro-T cells) interact with alpha 6 integrins present on vascular endothelium. Here, we demonstrate that anti-alpha 6 integrin antibodies reduced the number of thymocytes up to 80% in a congenic mouse model for thymus colonization by pro-T cells. In organotypic thymus cultures, the anti-alpha 6 integrin antibodies did not influence T cell development and proliferation. From this, we conclude that alpha 6 integrin participates in thymus homing. During mouse thymus ontogeny, alpha 6 integrin mRNA and protein expression was found as early as day 10 of development; at day 11, perithymic endothelial cells were alpha 6 integrin positive. Two alpha 6 integrin mRNA exist which are produced by alternative exon usage. The longer form, alpha 6 integrin, predominates during early embryonic stages, while the shorter alpha 6A form was present later during development. Although alpha 6 integrins can be displayed by immature thymocytes, strongest expression was found on intra- and perithymic vascular endothelium. These data suggest that alpha 6 integrins are involved in the homing of pro-T cells to the developing thymus by mediating adhesion of pro-T cells to the vascular endothelium.
在胚胎发生过程中,造血祖细胞对胸腺原基的定植取决于这些细胞与颈静脉内皮的黏附。此前,我们发现祖T细胞(pro-T细胞)与血管内皮上存在的α6整合素相互作用。在此,我们证明在一个用于pro-T细胞胸腺定植的同基因小鼠模型中,抗α6整合素抗体使胸腺细胞数量减少了80%。在器官型胸腺培养中,抗α6整合素抗体不影响T细胞的发育和增殖。由此我们得出结论,α6整合素参与胸腺归巢。在小鼠胸腺发育过程中,早在发育第10天就发现了α6整合素mRNA和蛋白表达;在第11天,胸腺周围内皮细胞α6整合素呈阳性。存在两种通过外显子选择性使用产生的α6整合素mRNA。较长形式的α6整合素在胚胎早期阶段占主导,而较短的α6A形式在发育后期出现。尽管未成熟胸腺细胞可表达α6整合素,但在胸腺内和胸腺周围血管内皮上发现其表达最强。这些数据表明,α6整合素通过介导pro-T细胞与血管内皮的黏附,参与pro-T细胞向发育中的胸腺归巢。