Dok-1 overexpression promotes development of γδ natural killer T cells

Eur J Immunol. 2012 Sep;42(9):2491-504. doi: 10.1002/eji.201242421. Epub 2012 Jul 16.

Abstract

In T cells, two members of the Dok family, Dok-1 and Dok-2, are predominantly expressed. Recent evidence suggests that they play a negative role in T-cell signaling. In order to define whether Dok proteins regulate T-cell development, we have generated transgenic mice overexpressing Dok-1 in thymocytes and peripheral T cells. We show that overexpression of Dok-1 retards the transition from the CD4(-) CD8(-) to CD4(+) CD8(+) stage. Moreover, there is a specific expansion of PLZF-expressing Vγ1.1(+) Vδ6.3(+) T cells. This subset of γδ T cells acquires innate characteristics including rapid IL-4 production following stimulation and requiring SLAM-associated adaptor protein (SAP) for their development. Moreover, Dok-1 overexpression promotes the generation of an innate-like CD8(+) T-cell population that expresses Eomesodermin. Altogether, these findings identify a novel role for Dok-1 in the regulation of thymic differentiation and in particular, in the development of PLZF(+) γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / metabolism*
  • Phosphoproteins / biosynthesis*
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Signaling Lymphocytic Activation Molecule Associated Protein

Substances

  • DNA-Binding Proteins
  • Dok1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Kruppel-Like Transcription Factors
  • Phosphoproteins
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA-Binding Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Zbtb16 protein, mouse