Activation of peripheral blood T cells by interaction and migration through endothelium: Role of lymphocyte function antigen-1/intercellular adhesionmolecule-1 and interleukin-15

Cell adhesion molecules have a key role in the migration of T cells to infl ammatory foci. However, the eff ect of the endothelial-lymphocyte interacti on on the activation of the latter cells remains unresolved. We have studie d the effect of resting and stimulated endothelial cells (ECs) on the activ ation of peripheral blood T cells (PBTLs), as assessed by the expression of CD69 and CD25 activation antigens. The incubation of PBTLs with tumor necr osis factor-alpha-activated EC monolayers, either alive or fixed, induced t he expression of CD69 but not CD25, preferentially in the CD8(+) CD45RO(+) cell subset. Furthermore, it induced the production of cytokines such as IF N-gamma, but not that of interleukin-2 (IL-2) and IL-4. EC treated with oth er stimuli such as IL-1 beta, IFN-gamma, or lipopolysaccharide also showed the same proactivatory effect on T cells. Lymphocyte activation was almost completely inhibited by blocking anti-CD18 and anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibodies (MoAbs), but only slightly a ffected by MoAbs against CD49d, vascular cell adhesion molecule-1, and anti -IL-15. In addition, the interaction of PBTL with immobilized ICAM-1 induce d CD69 expression in the same memory T-cell subset. IL-15 induced T-cell ac tivation with expression of CD69 and CD25, and production of IFN-gamma, and its effect was additive with that triggered by cell adhesion to either EC or immobilized ICAM-1. The transmigration of PBTLs through either confluent EC monolayers or ICAM-1-coated membranes also induced efficiently the expr ession of CD69. When IL-15 was used as chemoattractant in these assays, a f urther enhancement in CD69 expression was observed in migrated cells. Toget her these results indicate that stimulated endothelium may have an importan t role in T-cell activation, through the lymphocyte function antigen-1/ICAM -1 pathway, and that IL-15 efficiently cooperates in this phenomenon. These observations could account for the abundance of CD69(+) cells in the lymph ocytic infiltrates of several chronic inflammatory diseases. (C) 1999 by Th e American Society of Hematology.