Induction of interleukin-2 unresponsiveness and down-regulation of the JAK-STAT system upon activation through the T cell receptor

Eur J Immunol. 1997 Jul;27(7):1816-23. doi: 10.1002/eji.1830270733.

Abstract

Full activation of T cells with antigen (Ag) and antigen-presenting cells initiates effector functions and proliferation. When T cells are re-stimulated through the T cell receptor (TCR) after a primary stimulation with Ag, growth arrest and cell death are induced. Activation of a T cell clone by cross-linking of TCR induces interleukin (IL)-2 unresponsiveness and ultimately cell death. While the proliferative signal delivered by IL-2 induces c-myc, bcl-2 and cyclin D3 expression, the expression of bcl-2 and cyclin D3 is completely suppressed upon TCR stimulation. Furthermore, TCR stimulation induces a decrease in the protein levels of JAK3 and STAT5, suggesting that IL-2 unresponsiveness and growth arrest of T cells result from down-regulation of JAK3 and STAT5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / genetics
  • Cell Division / immunology
  • Clone Cells
  • Cyclin D3
  • Cyclins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / immunology*
  • Gene Expression Regulation / immunology
  • Immune Tolerance*
  • Interleukin-2 / physiology*
  • Janus Kinase 3
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Milk Proteins*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Antigen, T-Cell / physiology*
  • STAT5 Transcription Factor
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • Trans-Activators / metabolism*

Substances

  • Ccnd3 protein, mouse
  • Cyclin D3
  • Cyclins
  • DNA-Binding Proteins
  • Interleukin-2
  • Milk Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • STAT5 Transcription Factor
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • Jak3 protein, mouse
  • Janus Kinase 3