Transforming growth factor-beta1 suppresses interleukin-15-mediated interferon-gamma production in human T lymphocytes

Scand J Immunol. 1999 Dec;50(6):612-8. doi: 10.1046/j.1365-3083.1999.00635.x.


One of the most remarkable means by which tumour cells manage to evade recognition and elimination by the immune system is the release of immunosuppressive mediators, such as interleukin (IL)-10 or transforming growth factor-beta (TGF-beta). For antitumour immunotherapies to reach their full potential, cytokine cocktails will have to be custom-tailored to the tumour's individual cytokine microenvironment. One of the components of such a cytokine cocktail may be interleukin (IL)-15, which has demonstrated an excellent stimulatory potential of antitumour immunity. In an in vitro model, we have previously been able to show that the negative effects of IL-10 on IL-15-mediated cytotoxic T-cell activation can be outweighed by the addition of interleukin (IL)-12. The mechanism by which TGF-beta may influence the effect of IL-15 remains poorly understood, however. We have therefore taken our T-cell model further and have studied the effect of TGF-beta on IL-15-mediated interferon-gamma (IFN-gamma) production. In activated, IL-15-stimulated peripheral blood T lymphocytes, TGF-beta suppressed IFN-gamma mRNA and protein levels by approximately 75%. This effect was likewise observed on both CD4+ and CD8+ T cells and, in contrast to the effect of IL-10 in this system, could not be neutralized by the addition of IL-12. Thus, immunotherapy for TGF-beta-producing tumours may benefit from the addition of TGF-neutralizing activity rather than IL-12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Depression, Chemical
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-10 / pharmacology
  • Interleukin-12 / metabolism
  • Interleukin-12 / pharmacology
  • Interleukin-12 / physiology
  • Interleukin-15 / antagonists & inhibitors*
  • Interleukin-2 / pharmacology
  • Muromonab-CD3 / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / metabolism
  • Transforming Growth Factor beta / pharmacology*


  • Interleukin-15
  • Interleukin-2
  • Muromonab-CD3
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma