Regulation of TGF-beta response during T cell activation is modulated by IL-10

J Immunol. 2001 Jul 15;167(2):773-8. doi: 10.4049/jimmunol.167.2.773.

Abstract

TGF-beta1 is an important pleiotropic cytokine that has been described to have both stimulatory and inhibitory effects on cell growth and differentiation. For several cell types, the effect of TGF-beta1 was found to correlate with the differentiation stage of the cells and the presence of other cytokines. In this report, we address the influence of TGF-beta1 on CD4(+) T cell activation by evaluating the effect of TGF-beta1 on the proliferative and cytokine responses of purified resting and activated human or mouse CD4(+) T cells. TGF-beta1 inhibits proliferation and cytokine secretion on resting CD4(+) T cells but has no inhibitory effect on activated T cells. Moreover, TGF-beta1 unresponsiveness of activated T cells was correlated with a down-regulation in the expression of the TGF-beta receptor type II. Interestingly, IL-10 addition enhances TGF-beta receptor type II expression and restores TGF-beta responsiveness on activated T cells. These results indicated that TGF-beta responsiveness is sequentially regulated on T cells by the modulation of the of TGF-beta receptor type II chain expression. Moreover, we have identified a novel regulatory role of IL-10 on TGF-beta-dependent T cell growth that can explain the control of T cell activation on chronic vs acute inflammatory sites.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Clone Cells
  • Growth Inhibitors / physiology
  • Humans
  • Interleukin-10 / physiology*
  • Interphase / immunology
  • Lymphocyte Activation* / immunology
  • Mice
  • Mice, Transgenic
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Receptors, Transforming Growth Factor beta / genetics
  • Transcription, Genetic / immunology
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Adjuvants, Immunologic
  • Growth Inhibitors
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Interleukin-10
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II