Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.
Itk is a T cell protein tyrosine kinase (PTK) that, along with Btk and Tec, belongs to a family of cytoplasmic PTKs with N-terminal pleckstrin homology domains. Btk plays a critical role in B lymphocyte development. To determine whether Itk has an analogous role in T lymphocytes, we used gene targeting to prepare mice lacking expression of Itk. Such animals had decreased numbers of mature thymocytes, an effect most clearly observed in mice expressing T cell receptor (TCR) transgenes. Mature T cells from Itk-deficient mice had reduced proliferative responses to allogeneic MHC stimulation and to anti-TCR cross-linking, but responded normally to stimulation with phorbol ester plus ionomycin or with IL-2. These results provide genetic evidence that Itk is involved in T cell development and also suggest that Itk has an important role in proximal events in TCR-mediated signaling pathways.
Liao
X C
XC
Department of Microbiology and Immunology, University of California, San Francisco 94143-0414, USA.
Littman
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D016130:Immunophenotyping; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases