Dermal fibroblasts sustain proliferation of activated T cells via membrane-bound interleukin-15 upon long-term stimulation with tumor necrosis factor-alpha

J Invest Dermatol. 2001 Jan;116(1):102-9. doi: 10.1046/j.1523-1747.2001.00239.x.


In chronic inflammatory conditions, mononuclear cells infiltrate the connective tissue attracted by fibroblast-secreted chemokines. The role of fibroblasts in sustaining the lymphocyte immune response upon cellular infiltration is so far unresolved. We here report that, upon prolonged stimulation with tumor necrosis factor-alpha, dermal fibroblasts enhance proliferation of activated T cells whereas unstimulated fibroblasts do not. T cell growth stimulation requires cell contact of tumor necrosis factor-alpha stimulated fibroblasts to T cells and is not due to soluble factors. Growth stimulation is substantially blocked by neutralizing antibodies to interleukin-15. Fluorescence-activated cell sorter analyses revealed that tumor necrosis factor alpha stimulated fibroblasts expose interleukin-15 in a membrane-bound form on the cell surface whereas nonstimulated fibroblasts and interferon-gamma treated fibroblasts do not. The amount of membrane interleukin-15 increases with the duration of tumor necrosis factor-alpha stimulation for at least 3 d. Unstimulated fibroblasts, however, accumulate interleukin-15 in the cytoplasm. No interleukin-15 could be detected in the culture supernatant. Immunohistochemical analyses confirmed membrane interleukin-15 on dermal fibroblasts in discoid lupus erythematosus skin lesions whereas no membrane interleukin-15 was found on the surface of fibroblasts in healthy skin. We conclude that dermal fibroblasts upon long-term tumor necrosis factor-alpha stimulation during chronic inflammation are involved via membrane-bound interleukin-15 in stimulating proliferation of accumulated, activated T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Cell Division / physiology
  • Cell Membrane / chemistry
  • Fibroblasts / cytology*
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • Interleukin-15 / pharmacology*
  • Lupus Erythematosus, Discoid / pathology
  • Lymphocyte Activation / drug effects
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / cytology*
  • T-Lymphocytes / immunology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Antibodies
  • Interleukin-15
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha