GLYCAM-1, A PHYSIOLOGICAL LIGAND FOR L-SELECTIN, ACTIVATES BETA-2 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-lik e receptor, mediates the initial attachment of lymphocytes to high end othelial venules (HEV) in lymph nodes, A subsequent step involving the activation of beta 2 integrins has been proposed to facilitate firm a dhesion, but the activating signals are poorly understood. We report h ere 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 thr ough the beta 2 integrin pathway. Furthermore, GlyCAM-1 causes the rap id expression of a neoepitope on beta 2 integrins associated with a hi gh-avidity state. Naive (CD45RA(+)), but not memory (CD45R0(+)) lympho cytes, respond to L-selectin cross-linking or GlyCAM-1 treatment. Thus , the complexing of L-selectin by specific ligands may provide key sig nals to naive lymphocytes, contributing to their selective recruitment into peripheral lymphoid organs.