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Updated: Jul 23, 2026

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
Published on: August 13, 2013
Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet
Andrew T Miller1, Heather M Wilcox, Zhongbin Lai
1Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester 01655, USA.
Abstract:
The Tec family tyrosine kinase, Itk, is critical for PLC-gamma1 activation downstream of the TCR. Studies of Itk-/- mice have demonstrated a requirement for Itk in Th2 cytokine production and protective immunity to parasitic infections. Here we address the mechanism by which Itk regulates Th2 differentiation. We find that naive Itk-/- CD4+ T cells respond normally to cytokine skewing signals and can differentiate efficiently into either Th1 or Th2 lineage cells. In the absence of skewing cytokines, wild-type CD4+ T cells stimulated with low-avidity ligands preferentially express GATA-3 mRNA and differentiate into Th2 cells. Under these same stimulation conditions, Itk-/- T cells produce large amounts of T-bet mRNA and differentiate into IFN-gamma-producing cells. Furthermore, Itk is upregulated during Th2 differentiation, while Rlk, a related Tec kinase, disappears rapidly from differentiating Th2 cells. Together, these findings provide a molecular explanation for the essential role of Itk in Th2 differentiation.
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