title: Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis.
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-1 alpha were ineffective. Antibodies against CD69, LFA-1 or ICAM-1 significantly inhibited the ability of T cells to activate macrophages by cell contact.
authors.affiliation: Department of Immunology, University of Glasgow, UK.
authors.forename: I B
authors.initials: IB
authors.lastname: McInnes
authors.forename: B P
authors.initials: BP
authors.lastname: Leung
authors.forename: R D
authors.initials: RD
authors.lastname: Sturrock
authors.forename: M
authors.initials: M
authors.lastname: Field
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D013583:Synovial Membrane / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha