CD28-B7 INTERACTIONS PROMOTE T-CELL ADHESION

CD28 activation by antibody-mediated ligation has been shown to provid e an important co-stimulatory signal for T cell adhesion to purified p rotein ligands. However, the effect of CD28 ligation by one of its nat ural ligands, B7.1, on T cell adhesion to other cells has not been stu died. Therefore, in the present manuscript, we characterized the adhes ive interactions between human T cells and B7.1-transfected major hist ocompatibility complex class II+ and class II- melanoma cells. In our studies, human T cells and T cell clones adhered to B7.1-transfected m elanoma cells, but not to untransfected parental cells. The adhesive r eaction in this model was rapid, occurring within 15 min, and was inhi bited by anti-B7.1 antibody and soluble CTLA-4 immunoglobubulin. Antib ody inhibition studies demonstrated that adhesion between T cells and B7.1-transfected melanoma cells was mediated by interactions between L FA-1:ICAM-1 and CD2:LFA-3. Inhibition by pharmacological agents demons trated that the CD28-induced adhesion required specific intracellular signaling events. A protein kinase C inhibitor, staurosporin, signific antly inhibited T cell binding to transfected melanoma cells, while cy closporin A and wortmannin, an inhibitor of phosphatidylinositol-3-kin ase, did not. These results suggest that the presence of B7 on various cell populations may activate lymphocytes to adhere better, thus prom oting activation, cytolysis, and migration.