Itk and Th2 responses: action but no reaction.
The Tec family tyrosine kinase, Itk, was initially characterized as a crucial component of T-cell receptor signaling pathways resulting in phospholipase C-gamma1 activation and actin polymerization. In 1999, a seminal report by Fowell, Locksley and colleagues demonstrated that, in CD4+ T cells, Itk-dependent signals are differentially required for T-helper (Th)2 versus Th1 differentiation and effector function. These findings launched a series of in vitro and in vivo studies addressing the molecular defects of Itk-/- CD4+ T cells, and the impaired immune responses of intact Itk-deficient mice. While demonstrating a bias against Th2 differentiation, overall these experiments have indicated that the most significant failing is an inability of Itk-/- CD4+ T cells to produce Th2 cytokines in a recall response, rather than an absolute defect in Th2 differentiation by T cells lacking Itk. In this review, we discuss the pathways by which Itk might impact the differentiation of Th cells.
Kosaka
Yoko
Y
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Felices
Martin
M
Berg
Leslie J
LJ
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000201:enzymology* / Q000276:immunology*
D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase