Anergic T cells are defective in both jun NH2-terminal kinase and mitogen-activated protein kinase signaling pathways

doi:10.1084/jem.183.5.2017

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Anergic T cells are defective in both jun NH2-terminal kinase and mitogen-activated protein kinase signaling pathways

DR DeSilva, WS Feeser, EJ Tancula and PA Scherle
Dupont Merck Pharmaceutical Company, Inflammatory Diseases Research, Wilmington, Delaware 19880-0400, USA.

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.
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