INDUCTION OF T-CELL ADHESION TO EXTRACELLULAR-MATRIX OR ENDOTHELIAL-CELL LIGANDS BY SOLUBLE OR MATRIX-BOUND INTERLEUKIN-7

The putative effects of interleukin (IL)-7, operating in the context o f extracellular matrix (ECM), on the adhesion of human T cells were ex amined. Recombinant human IL-7 was found to bind ECM or fibronectin (F N) with IC50 values of 10-100 nM. Nanogram amounts of both soluble and , especially, FN- or ECM-bound IL-7, which differentially affected the morphologies of FN-adherent T cells, induced the adhesion of resting CD4(+) and CD8(+) T cells in dose-dependent and beta 1 integrin-depend ent manners. Under static and flow conditions, soluble IL-7 also induc ed the binding of unstimulated T cells to vascular cell adhesion molec ule-1, suggesting that this cytokine can also modulate integrin bindin g to endothelial cell ligands. The effects of affinity modulation by I L-7 of FN-specific beta 1 integrins depend on the presence of soluble FN, which inhibited T cell adhesion to FN induced by FN-bound IL-7 or by an integrin-specific affinity-modulating monoclonal antibody, but n ot by soluble IL-7 or phorbol 12-myristate 13-acetate. These findings provide an example of a major ECM integrin ligand, FN, which is capabl e of modulating its adhesive interactions with specific immune cells b y associating with and presenting a cytokine in a bio-active state.