GlyCAM-1, a physiologic ligand for L-selectin, activates β2 integrins on naive peripheral lymphocytes

Naive T cells are selectively recruited from the blood into peripheral lymph nodes during lymphocyte recirculation. L-selectin, a lectin-like receptor, mediates the initial attachment of lymphocytes to high endothelial venules (HEV) in lymph nodes. A subsequent step involving the activation of β2 integrins has been proposed to facilitate firm adhesion, but the activating signals are poorly understood. We report here that here that either antibody-mediated cross-linking of L-selectin on human lymphocytes or treatment of the cells with GlyCAM-1, an HEV-derived, secreted ligand for L- selectin, stimulates their binding to ICAM-1 through the β2 integrin pathway. Furthermore, GlyCAm-1 causes the rapid expression of a neoepitope on β2 integrins associated with a high-avidity state. Naive (CD45RA⁺), but not memory (CD45RO⁺) lymphocytes, respond to L-selectin cross-linking or GlyCAM- 1 treatment. Thus, the complexing of L-selectin by specific ligands may provide key signals to naive lymphocytes, contributing to their selective recruitment into peripheral lymphoid organs.