Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction

Nat Immunol. 2002 Jul;3(7):652-8. doi: 10.1038/ni807. Epub 2002 Jun 10.


Type 1 helper T (T(H)1) cells are essential for cellular immunity, but their ontogeny, maturation and durability remain poorly understood. By constructing a dominant-negative form of T-bet, we were able to determine the role played by this lineage-inducing trans-activator in the establishment and maintenance of heritable T(H)1 gene expression. Optimal induction of interferon-gamma (IFN-gamma) expression required genetic interaction between T-bet and its target, the homeoprotein Hlx. In fully mature T(H)1 cells, reiteration of IFN-gamma expression and stable chromatin remodeling became relatively independent of T-bet activity and coincided with demethylation of DNA. In contrast, some lineage attributes, such as expression of IL-12R beta 2 (interleukin 12 receptor beta 2), required ongoing T-bet activity in mature T(H)1 cells and their progeny. These findings suggest that heritable states of gene expression might be maintained by continued expression of the inducing factor or by a mechanism that confers a stable imprint of the induced state.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chromatin / physiology
  • DNA Methylation
  • Gene Expression*
  • Homeodomain Proteins / genetics*
  • Humans
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-12
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / physiology
  • T-Box Domain Proteins
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Transcriptional Activation


  • Chromatin
  • HLX protein, human
  • Hlx protein, mouse
  • Homeodomain Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Recombinant Fusion Proteins
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Trans-Activators
  • Transcription Factors
  • Interferon-gamma