A comprehensive review of the phenotype and function of antigen-specific immunoregulatory double negative T cells

J Autoimmun. 2013 Feb;40:58-65. doi: 10.1016/j.jaut.2012.07.010. Epub 2012 Aug 19.


Double negative T cells that lack the expression of both CD4 and CD8 T cell co-receptors exhibit a most unique antigen-specific immunoregulatory potential first described over a decade ago. Due to their immunoregulatory function, this rare T cell population has been studied in both mice and humans for their contribution to peripheral tolerance and disease prevention. Consequently, double negative cells are gaining interest as a potential cellular therapeutic. Herein, we review the phenotype and function of double negative T cells with emphasis on their capacity to induce antigen-specific immune tolerance. While the phenotypic and functional similarities between double negative T cells identified in mouse and humans are highlighted, we also call attention to the need for a specific marker of double negative T cells, which will facilitate future studies in humans. Altogether, due to their unique properties, double negative T cells present a promising therapeutic potential in the context of various disease settings.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD4 Antigens / metabolism*
  • CD8 Antigens / metabolism*
  • Humans
  • Immune Tolerance*
  • Mice
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*


  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Antigen, T-Cell