THE ROLE OF INTERLEUKIN-15 IN T-CELL MIGRATION AND ACTIVATION IN RHEUMATOID-ARTHRITIS

Interleukin 15 (IL-15) is a novel cytokine with interleukin-2-like act ivity. It is also a potent T-lymphocyte chemoattractant. Rheumatoid ar thritis (RA) is a chronic inflammatory disease characterized by the pr esence of activated T lymphocytes, macrophages and synoviocytes in the synovial membrane. The mechanisms of T-cell activation in RA are curr ently unclear. We report the presence of high concentrations of IL-15 in rheumatoid arthritis (RA) synovial fluid and have demonstrated its expression in the synovial membrane lining layer by immunohistochemist ry. RA synovial fluids were found to contain chemotactic activity, whi ch was attributable in part to the presence of IL-15. Moreover, in a m urine model, injection of recombinant IL-15 was found to induce a loca l tissue inflammatory infiltrate consisting predominantly of T lymphoc ytes. Synovial fluid T lymphocytes proliferate in response to IL-15, d emonstrating that continued responsiveness to IL-15 is a feature of T cells after entry into the synovial compartment, These data suggest th at IL-15 can recruit and activate T lymphocytes into the synovial memb rane, thereby contributing to RA pathogenesis.