The Tec family tyrosine kinase, Itk, was initially characterized as a crucial component of T-cell receptor signaling pathways resulting in phospholipase C-γ1 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.
Bibliographical noteFunding Information:
We acknowledge the following sources of support: NIH grants AI37584, AI46564 and AI66118, and a grant from the Center for Disease Control, CI000101. These sources had no role in the preparation or submission of this article.