Tec kinase Itk in gammadeltaT cells is pivotal for controlling IgE production in vivo

Proc Natl Acad Sci U S A. 2009 May 19;106(20):8308-13. doi: 10.1073/pnas.0808459106. Epub 2009 May 1.

Abstract

In conventional alphabeta T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates alphabeta T cell development, lineage commitment, and effector function. A well established feature of Itk(-/-) mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is gammadelta T cells, as normal IgE levels are observed in Itk(-/-)Tcrd(-/-) mice. When stimulated through the gammadelta TCR, Itk(-/-) gammadelta T cells produce high levels of Th2 cytokines, but diminished IFNgamma. In addition, activated Itk(-/-) gammadelta T cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that gammadelta T cells numbers are increased in Itk(-/-) mice, most notably the Vgamma1.1(+)Vdelta6.3(+) subset that represents the dominant population of gammadelta NKT cells. Itk(-/-) gammadelta NKT cells also have increased expression of PLZF, a transcription factor required for alphabeta NKT cells, indicating a common molecular program between alphabeta and gammadelta NKT cell lineages. Together, these data indicate that Itk signaling regulates gammadelta T cell lineage development and effector function and is required to control IgE production in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes
  • Cell Lineage
  • Cytokines / biosynthesis
  • Immunoglobulin Class Switching
  • Immunoglobulin E / biosynthesis*
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Natural Killer T-Cells / cytology
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology*
  • Th2 Cells

Substances

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