DEVELOPMENTAL REGULATION OF VASCULAR ADDRESSIN EXPRESSION - A POSSIBLE ROLE FOR SITE-ASSOCIATED ENVIRONMENTS

Tissue selective traffic of lymphocytes into different lymphoid organs is mediated by adherence of blood borne lymphocytes to specialized endothelial cells lining the high endothelial venules (HEV) in lymphoid organs. Lymphocytes discriminate between HEV in peripheral lymph nodes and in mucosal lymphoid tissues by means of membrane associated lymphocyte homing receptors adhering to their putative HEV ligands, the vascular addressins. The expression of particular vascular addressins on HEV is site- or tissue-selective and may be directed by factors unique to a specific location or lymph node environment. In this study we investigated the impact of regional environments on lymph node HEV differentiation and function. Experimentally, this problem was approached by the transplantation of lymph nodes from one region to a second region. The sites selected for receipt of tissues were the mesentery, a mucosal site, and the popliteal fossa, a peripheral site. We found that the phenotype of lymph node HEV following transplantation was influenced by both donor age and transplantation site. The transplantation site could influence vascular addressin expression, when tissues were obtained from late fetal or early neonatal donors and not when obtained from adult donors. Transplanted adult tissues retained their pre-transplantation vascular addressin expression phenotype regardless of transplantation site. Thus the endothelium within adult lymph nodes may be committed to expression of a particular addressin or addressins during lymph node development. It is also possible that regulatory cells or structures present within lymph nodes at the time of transplantation direct vascular addressin expression following tissue engraftment. These studies show that regional environments of the lymph nodes could play a role in HEV differentiation and function during lymph node development.