Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-α production in rheumatoid arthritis

McInnes, I. B. , Leung, B. P., Sturrock, R. D., Field, M. and Liew, F. Y. (1997) Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-α production in rheumatoid arthritis. Nature Medicine, 3(2), pp. 189-195. (doi:10.1038/nm0297-189) (PMID:9018238)

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Abstract

Tumor necrosis factor-alpha occupies a central role in rheumatoid arthritis (RA) pathogenesis. We now report that Interleukin-15 (IL-15) can induce TNF-alpha production in RA through activation of synovial T cells. Peripheral blood (PB) T cells activated by IL-15 induced significant TNF-alpha production by macrophages via a cell-contact-dependent mechanism. Freshly isolated RA synovial T cells possessed similar capability, and in vitro, IL-15 was necessary to maintain this activity. IL-15 also induced direct TNF-alpha production by synovial T cells. In contrast, IL-2 induced significantly lower TNF-alpha production in either cell-contact-dependent or direct culture, and IL-8 and MIP-1alpha were ineffective. Antibodies against C069, LFA-1 or ICAM-1 significantly inhibited the ability of T cells to activate macrophages by cell contact.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Sturrock, Professor Roger and Field, Dr Max and Leung, Dr Bernard
Authors: McInnes, I. B., Leung, B. P., Sturrock, R. D., Field, M., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Nature Medicine
Publisher:Nature Publishing Group
ISSN:1078-8956
ISSN (Online):1546-170X

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