The p38 mitogen-activated protein kinase pathway in activated and anergic Th1 cells

Cell Immunol. 1997 Sep 15;180(2):116-23. doi: 10.1006/cimm.1997.1182.

Abstract

Stimulation of T cells through the TCR leads to activation of the mitogen-activated protein kinase (MAPK) family members ERK (extracellular signal-regulated kinase) and JNK (jun NH2-terminal kinase). These kinases act in synergy to increase the activity of the transcription factor AP-1 which is involved in the transcriptional upregulation of IL-2. Recently a third MAPK member, p38, has been identified. The effects of T cell activation on this pathway have not yet been elucidated. Using two murine Th1 clones, we demonstrate that the p38 pathway is induced upon anti-CD3 plus anti-CD28 crosslinking or PMA plus ionomycin stimulation. p38 activity was induced fully by anti-CD3 or PMA alone and is not enhanced by costimulation even at low levels of TCR signaling. p38 activity peaked at 20 min and was significantly decreased by 2 hr. Anergic (tolerant) Th1 cells showed decreased p38 activity as well as decreased ERK and JNK activities even though levels of these proteins remained unchanged.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cells, Cultured
  • Clonal Anergy*
  • Enzyme Activation
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction
  • Th1 Cells / enzymology*
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Interleukin-2
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Transcription Factor AP-1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases