Transforming growth factor-beta promotes 'death by neglect' in post-activated human T cells

Immunology. 2001 Mar;102(3):310-6. doi: 10.1046/j.1365-2567.2001.01185.x.

Abstract

Transforming growth factor-beta (TGF-beta) is central to the wound repair processes that follow local trauma and inflammation. In order to mimic the early events of wound-healing, we studied the effects of TGF-beta on mitogen-stimulated peripheral blood cells. TGF-beta added at the initiation of mitogenesis did not significantly alter T-cell activation, proliferation, CD45 isoform switching, or activation-induced cell death. By contrast, TGF-beta added 72 hr post-activation (or later) enhanced the cumulative increase in apoptotic T cells. TGF-beta had no effect on mitogen-induced up-regulation of Fas (CD95) or Fas ligand and did not enhance killing of the Fas-sensitive Jurkat cell line by activated T cells. Furthermore, TGF-beta had no direct effect on levels of mRNA for members of the bcl family (bcl-X, bfl-1, bik, bak, bax, bcl-2 and mcl-1). These findings suggest that TGF-beta does not directly induce apoptosis via the Fas system or by direct effects on bcl proteins. However, interleukin-2, which can 'rescue' lymphocytes from spontaneous apoptosis due to cytokine deprivation, abolished the pro-apoptotic effects of TGF-beta on post-activated T cells, thus demonstrating that TGF-beta increases the cytokine-dependence of T cells for survival. We propose a novel role for TGF-beta in the suppression of inflammation by promoting the elimination of post-activated T cells once the initiating stimulus has been resolved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Cell Culture Techniques
  • Cell Division / immunology
  • Cell Survival / immunology
  • Fas Ligand Protein
  • Humans
  • Interleukin-2 / immunology
  • Jurkat Cells / immunology
  • Leukocyte Common Antigens / metabolism
  • Ligands
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / metabolism
  • Phytohemagglutinins / immunology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / immunology*
  • fas Receptor / metabolism

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-2
  • Ligands
  • Membrane Glycoproteins
  • Phytohemagglutinins
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta
  • fas Receptor
  • Leukocyte Common Antigens