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-Chain Administration Prevents Murine Collagen-Induced Arthritis: A Role for IL-15 in Development of Antigen-Induced Immunopathology1
* Department of Immunology and Centre for Rheumatic Diseases, University of Glasgow, United Kingdom
IL-15 has recently been detected in the synovium of patients with
rheumatoid arthritis. IL-15-activated T cells induce significant
TNF-
synthesis by macrophages via a cell contact-dependent
mechanism, suggesting a key regulatory role for IL-15. Here, we report
that the administration of a soluble fragment of IL-15R into DBA/1
mice, profoundly suppressed the development of collagen-induced
arthritis. This was accompanied in vitro by marked reductions in
Ag-specific proliferation and IFN-
synthesis by spleen cells from
treated mice compared with control mice and in vivo by a significant
reduction in serum anti-collagen Ab levels. These data directly
demonstrate a pivotal role for IL-15 in the development of inflammatory
arthritis and also suggest that antagonists to IL-15 may have
therapeutic potential in rheumatic diseases.
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T. A. Fehniger, H. Yu, M. A. Cooper, K. Suzuki, M. H. Shah, and M. A. Caligiuri Cutting Edge: IL-15 Costimulates the Generalized Shwartzman Reaction and Innate Immune IFN-{gamma} Production In Vivo J. Immunol., February 15, 2000; 164(4): 1643 - 1647. [Abstract] [Full Text] [PDF]
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H. Yamada, T. Nakamura, G. Matsuzaki, Y. Iwamoto, and K. Nomoto TCR-Independent Activation of Extrathymically Developed, Self Antigen-Specific T Cells by IL-2/IL-15 J. Immunol., February 15, 2000; 164(4): 1746 - 1752. [Abstract] [Full Text] [PDF]
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