Nature Medicine
2, 175 - 182 (1996)
doi:10.1038/nm0296-175
The role of interleukin−15 in T−cell migration and activation in rheumatoid arthritisIain B. McInnes1, 2, Jamil Al-Mughales1, Max Field2, Bernard P. Leung1, Fang-ping Huang1, Richard Dixon3, Roger D. Sturrock2, Peter C. Wilkinson1
& Foo Y. Liew1
1Department of Immunology, University Department of Medicine, University of Glasgow, Glasgow, Gl1 6NT, UK
2Centre for Rheumatic Diseases, University Department of Medicine, University of Glasgow, Glasgow, Gl1 6NT, UK
3Yamanouchi Research Institute, Littlemore Hospital, Oxford, OX4 4XN, UK Correspondence should be addressed to F.Y.L. Interleukin 15 (IL−15) is a novel cytokine with interleukin−2−like activity. It is also a potent T−lymphocyte chemoattractant. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the presence of activated T lymphocytes, macrophages and synoviocytes in the synovial membrane. The mechanisms of T−cell activation in RA are currently 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 immunohistochemistry. RA synovial fluids were found to contain chemotactic activity, which was attributable in part to the presence of IL−15. Moreover, in a murine model, injection of recombinant IL−15 was found to induce a local tissue inflammatory infiltrate consisting predominantly of T lymphocytes. Synovial fluid T lymphocytes proliferate in response to IL−15, demonstrating that continued responsiveness to IL−15 is a feature of T cells after entry into the synovial compartment. These data suggest that IL−15 can recruit and activate T lymphocytes into the synovial membrane, thereby contributing to RA pathogenesis.
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