Defective Fas ligand expression and activation-induced cell death in the absence of IL-2-inducible T cell kinase
KeywordsAnimals; *Apoptosis; CD4-Positive T-Lymphocytes; Calcium; Cells, Cultured; Cytochrome c Group; Fas Ligand Protein; Genes, T-Cell Receptor; Interleukin-2; *Lymphocyte Activation; MAP Kinase Signaling System; Membrane Glycoproteins; Mice; Mice, Knockout; Mice, Transgenic; Mitogen-Activated Protein Kinases; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell; Transcription Factors; Transcription, Genetic; Up-Regulation
Medicine and Health Sciences
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AbstractThe Tec family tyrosine kinase, IL-2-inducible T cell kinase (Itk), plays an important role in TCR signaling. Studies of T cells from Itk-deficient mice have demonstrated that Itk is critical for the activation of phospholipase-Cgamma1, leading to calcium mobilization in response to TCR stimulation. This biochemical defect results in reduced IL-2 production by Itk-deficient T cells. To further characterize the downstream effects of the Itk deficiency, we crossed Itk-/- mice to a TCR-transgenic line and examined T cell responses to stimulation by peptide plus APC. These studies show that Itk is required for maximal activation of early growth responses 2 and 3 and Fas ligand transcription after TCR stimulation. These transcriptional defects lead to reduced activation-induced cell death of stimulated Itk-/- T cells, both in vitro and in vivo. Together these studies define an important role for Itk in TCR signaling, leading to cytokine gene expression and activation-induced cell death.
J Immunol. 2002 Mar 1;168(5):2163-72.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34210