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Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical Center, Worcester, MA 01655
The 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-C
1, 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.
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D. Tokita, M. Shishida, H. Ohdan, T. Onoe, H. Hara, Y. Tanaka, K. Ishiyama, H. Mitsuta, K. Ide, K. Arihiro, et al. Liver Sinusoidal Endothelial Cells That Endocytose Allogeneic Cells Suppress T Cells with Indirect Allospecificity J. Immunol., September 15, 2006; 177(6): 3615 - 3624. [Abstract] [Full Text] [PDF]
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S. R. Mayack and L. J. Berg Cutting Edge: An Alternative Pathway of CD4+ T Cell Differentiation Is Induced Following Activation in the Absence of {gamma}-Chain-Dependent Cytokine Signals J. Immunol., February 15, 2006; 176(4): 2059 - 2063. [Abstract] [Full Text] [PDF]
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L. O. Atherly, M. A. Brehm, R. M. Welsh, and L. J. Berg Tec Kinases Itk and Rlk Are Required for CD8+ T Cell Responses to Virus Infection Independent of Their Role in CD4+ T Cell Help J. Immunol., February 1, 2006; 176(3): 1571 - 1581. [Abstract] [Full Text] [PDF]
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D. Dombroski, R. A. Houghtling, C. M. Labno, P. Precht, A. Takesono, N. J. Caplen, D. D. Billadeau, R. L. Wange, J. K. Burkhardt, and P. L. Schwartzberg Kinase-Independent Functions for Itk in TCR-Induced Regulation of Vav and the Actin Cytoskeleton J. Immunol., February 1, 2005; 174(3): 1385 - 1392. [Abstract] [Full Text] [PDF]
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J. A. Deane, M. J. Trifilo, C. M. Yballe, S. Choi, T. E. Lane, and D. A. Fruman Enhanced T Cell Proliferation in Mice Lacking the p85{beta} Subunit of Phosphoinositide 3-Kinase J. Immunol., June 1, 2004; 172(11): 6615 - 6625. [Abstract] [Full Text] [PDF]
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