GlyCAM-1, a physiologic ligand for l-selectin, activates beta 2 integrins in naive T lymphocytes

Naive T cells (CD45RA+) are selectively recruited to peripheral lymph nodes during lymphocyte recirculation. In this multistep process, L-selectin, a member of the family of carbohydrate-binding receptors involved in leukocyte-endothelial interactions, mediates the attachment oflymphocytes to high endothelial venules (HEV) in lymph nodes. In contrast to other HEV-associated ligands for L-selectin such as CD34 and MAdCAM-I, GlyCAM-1 is secreted without any apparent association with the vascular luminal surface. These observations suggest that GlyCAM-1 may perform a signaling role rather than a direct pro-adhesive function. We report here that either antibody-mediated crosslinking of L-selectin on peripheral lymphocytes or treatment of these cells with purified GlyCAM-1 stimulates their binding to ICAM-1 via beta 2 integrins. Furthermore, GlyCAM-1 causes the rapid expression (within seconds) of the mab24-defined neoepitope on beta 2 integrins that is associated with a high-avidity binding state. Strikingly, the naive population but not the memory population (CD45RO+) oflymphocytes responds to either crosslinking L-selectin or GlyCAM-I treatment. These results suggest that ligation of L-selectin by GlyCAM-1 or other ligands may provide key signals to the lymphocyte leading to the selective recruitment of naive cells into peripheral lymph nodes.