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

Nat Med. 1997 Feb;3(2):189-95. doi: 10.1038/nm0297-189.


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.

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-15 / pharmacology*
  • Lymphocyte Activation / drug effects*
  • Synovial Membrane / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Interleukin-15
  • Tumor Necrosis Factor-alpha