Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production

Blood. 2009 Jul 16;114(3):564-71. doi: 10.1182/blood-2008-12-196345. Epub 2009 May 14.


The Tec kinase Itk is critical for the development of alphabeta T cells as well as differentiation of CD4(+) T cells into Th2 cells. Itk null mice have defects in the production of Th2 cytokines; however, they paradoxically have significant elevations in serum IgE. Here we show that Itk null mice have increased numbers of gammadelta T cells in the thymus and spleen. This includes elevated numbers of CD4(+) gammadelta T cell, the majority of which carry the Vgamma1.1 and Vdelta6.2/3 gammadelta T-cell receptor with a distinct phenotype. The development of these CD4(+) gammadelta T cells is T cell intrinsic, independent of either major histocompatibility complex class I or class II, and is favored during development in the absence of Itk. Itk null CD4(+) gammadelta T cells secrete significant amounts of Th2 cytokines and can induce the secretion of IgE by wild-type B cells. Our data indicate that Itk plays important role in regulating gammadelta T-cell development and function. In addition, our data indicate that the elevated IgE observed in Itk-deficient mice is due in part to the enhanced development of CD4(+) gammadelta T cells in the absence of Itk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • Cell Proliferation*
  • Cytokines
  • Immunoglobulin E / biosynthesis*
  • Mice
  • Mice, Knockout
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, T-Cell, gamma-delta*
  • Spleen / cytology
  • Th2 Cells
  • Thymus Gland / cytology


  • Cytokines
  • Receptors, Antigen, T-Cell, gamma-delta
  • Immunoglobulin E
  • Protein-Tyrosine Kinases
  • emt protein-tyrosine kinase