Lymphocyte adhesion to endothelial cells in vitro: models for the study of normal lymphocyte recirculation and lymphocyte emigration into chronic inflammatory lesions.

Abstract

Lymphocytes preferentially leave the bloodstream to enter secondary lymphoid organs or sites of inflammation by first adhering to, and then migrating through, the walls of specialized postcapillary venules known as high endothelial venules. To study the initial adhesion event between lymphocytes and endothelial cells, two different in vitro assays have been developed. In the first, lymphocytes are incubated on frozen sections of lymphoid organs or other tissues. Under certain conditions, lymphocytes specifically bind to the endothelial cells of high endothelial venules in such sections. The results of monoclonal antibody inhibition studies have suggested that endothelial cells at various lymphoid organs, and at certain inflammatory lesions, may express organ-specific ligands on their surface, which bind to corresponding organ-specific "homing receptors" on the lymphocytes. The second assay measures the adhesion of lymphocytes to confluent monolayers of viable, cultured endothelial cells. Because pretreatment of such cell monolayers with a number of cytokines produced at inflammatory sites stimulates an increase in the adhesiveness of the cells for lymphocytes, it has been suggested that such cytokine-induced increases in endothelial cell adhesiveness may be important in the induction of lymphocyte traffic into such lesions. Unlike the homing receptor type of binding described above, the cytokine-induced increase in lymphocyte-endothelial cell adhesion is presumably non-tissue-specific. Results of monoclonal antibody inhibition studies in this system have suggested that at least two ligand-receptor interactions may be involved. Monoclonal antibodies to the lymphocyte function-associated antigen-1 greatly inhibited the adhesion of T cells to untreated endothelial cells, but had little or no inhibitory effect on T-cell adhesion to cytokine-treated endothelial cells.