ALPHA(6) INTEGRINS PARTICIPATE IN PRO-T CELL HOMING TO THE THYMUS

During embryogenesis, colonization of the thymic rudiment by hemopoiet ic progenitor cells depends on the adhesion of these cells to the jugu lar endothelium. Previously, we showed that progenitor T cells (pro-T cells) interact with alpha(6) integrins present on vascular endotheliu m. Here, we demonstrate that anti-alpha(6) integrin antibodies reduced the number of thymocytes up to 80% in a congenic mouse model for thym us colonization by pro-T cells. In organotypic thymus cultures, the an ti-alpha(6) integrin antibodies did not influence T cell development a nd proliferation. From this, we conclude that alpha(6) integrin partic ipates in thymus homing. During mouse thymus ontogeny, alpha(6) integr in mRNA and protein expres sion was found as early as day 10 of develo pment; at day 11, perithymic endothelial cells were alpha(6), integrin positive. Two alpha(6) integrin mRNA exist which are produced by alte rnative exon usage. The longer form, alpha(6) integrin, predominates d uring early embryonic stages, while the shorter alpha(6) form was pres ent later during development. Although alpha(6) integrins can be displ ayed 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 endotheliu m.