CD28 costimulation is required not only to induce IL-12 receptor but also to render janus kinases/STAT4 responsive to IL-12 stimulation in TCR-triggered T cells

Eur J Immunol. 2001 May;31(5):1456-64. doi: 10.1002/1521-4141(200105)31:5<1456::AID-IMMU1456>3.0.CO;2-A.


The activation of resting T cells for the acquisition of various functions depends on whether CD28 costimulatory signals are provided upon T cell receptor stimulation. Here, we investigated how CD28 costimulation functions to allow TCR-triggered resting T cells to acquire IL-12 responsiveness. When T cells are stimulated with low doses of anti-CD3 mAb, CD28 costimulation was required for the optimal levels of IL-12 receptor (IL-12R) expression. However, stimulation of T cells with high doses of anti-CD3 alone induced comparable levels of IL-12R expression to those induced upon CD28 costimulation. Nevertheless, there was a substantial difference in IL-12 responsiveness between these two groups of T cells: compared to anti-CD28-costimulated T cells, T cells that were not costimulated with anti-CD28 exhibited decreased levels of Janus kinases (JAK) JAK2/TYK2 and STAT4 phosphorylation and IFN-y production following IL-12 stimulation. Importantly, STAT6 phosphorylation following IL-4 stimulation was not decreased in anti-CD28-uncostimulated T cells. These resutls indicate that CD28 costimulation not only contributes to up-regulating IL-12R expression but is also required to render JAKs/STAT4 responsive to IL-12 stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CD28 Antigens / metabolism*
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation / drug effects
  • Flow Cytometry
  • Interferon-gamma / metabolism
  • Interleukin-12 / pharmacology*
  • Interleukin-4 / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT6 Transcription Factor
  • Signal Transduction / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / metabolism
  • Trans-Activators / metabolism*


  • CD28 Antigens
  • DNA-Binding Proteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT6 Transcription Factor
  • Stat4 protein, mouse
  • Stat6 protein, mouse
  • Trans-Activators
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases