Abstract
T helper type 1 cells (Th1) become anergic when stimulated through the antigen receptor in the absence of costimulation. They do not produce IL-2 or proliferate in response to subsequent stimulation. Previous studies have indicated that anergic T cells are defective in the trnsactivational activity of the transcription factor, AP-1, which is required for optimal IL-2 transcription. Using two murine Th1 cell clones, we demonstrate that anergic Th1 cells have defects in both jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activities. These kinases have been shown to be important for the upregulation of AP-1 activity. Furthermore, our data show that ERK and JNK activities are restored when anergy is induced in the presence of the protein synthesis inhibitor cycloheximide, or when anergic T cells are allowed to proliferate in response to exogenous IL-2. These treatments have previously been shown to prevent or reverse the anergic state. Our results suggest that defects in both JNK and ERK may result in the decreased AP-1 activity and the reduced IL-2 transcription observed in anergic T cells.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies
-
CD3 Complex / immunology
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
-
Cells, Cultured
-
Clonal Anergy*
-
Cycloheximide / pharmacology
-
Influenza A virus / immunology
-
Interleukin-2 / biosynthesis
-
Interleukin-2 / pharmacology
-
Ionomycin / 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*
-
Phosphorylation
-
Protein Serine-Threonine Kinases / metabolism
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-raf
-
Signal Transduction
-
Spleen / immunology
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / immunology*
-
T-Lymphocytes / physiology
-
Tetradecanoylphorbol Acetate / pharmacology
-
Transcription Factor AP-1 / metabolism
Substances
-
Antibodies
-
CD3 Complex
-
Interleukin-2
-
Proto-Oncogene Proteins
-
Transcription Factor AP-1
-
Ionomycin
-
Cycloheximide
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-raf
-
Calcium-Calmodulin-Dependent Protein Kinases
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases
-
Tetradecanoylphorbol Acetate