Helios deficiency has minimal impact on T cell development and function

J Immunol. 2009 Aug 15;183(4):2303-11. doi: 10.4049/jimmunol.0901407. Epub 2009 Jul 20.

Abstract

Helios is a member of the Ikaros family of zinc finger transcription factors. It is expressed mainly in T cells, where it associates with Ikaros-containing complexes and has been proposed to act as a rate-limiting factor for Ikaros function. Overexpression of wild-type or dominant-negative Helios isoforms profoundly alters alphabeta T cell differentiation and activation, and endogenous Helios is expressed at strikingly high levels in regulatory T cells. Helios has also been implicated as a tumor suppressor in human T cell acute lymphoblastic leukemias. These studies suggest a central role for Helios in T cell development and homeostasis, but whether this protein is physiologically required in T cells is unclear. We report herein that inactivation of the Helios gene by homologous recombination does not impair the differentiation and effector cell function of alphabeta and gammadelta T cells, NKT cells, and regulatory T cells. These results suggest that Helios is not essential for T cells, and that its function can be compensated for by other members of the Ikaros family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics*
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Clone Cells
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Gene Silencing / immunology
  • Ikaros Transcription Factor / genetics
  • Ikaros Transcription Factor / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Multigene Family / immunology
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics*
  • Transcription Factors / physiology

Substances

  • DNA-Binding Proteins
  • IKZF1 protein, human
  • Receptors, Antigen, T-Cell
  • Transcription Factors
  • Zfpn1a1 protein, mouse
  • Zfpn1a2 protein, mouse
  • Ikaros Transcription Factor