T-bet, a Th1 transcription factor regulates the expression of Tim-3

Eur J Immunol. 2010 Mar;40(3):859-66. doi: 10.1002/eji.200939842.


T-cell immunoglobulin, mucin domain-3 (Tim-3) is a membrane protein expressed at late stages of IFN-gamma secreting CD4(+) Th1 cell differentiation and constitutively on DC. Ligation of Tim-3 on Th1 cells terminates Th1 immune responses. In addition, Tim-3 plays a role in tolerance induction, although the mechanism by which this is accomplished has yet to be elucidated. While it is clear that Tim-3 plays an important role in the immune system, little is known regarding the molecular pathways that regulate Tim-3 expression. In the current study, we examine the role of Th1-associated transcription factors in regulating Tim-3 expression. Our experiments reveal that Tim-3 expression is regulated by the Th1-specific transcription factor T-bet. This introduces a novel paradigm into the generation of a Th1 response, whereby a transcription factor responsible for effector Th1 cell differentiation also increases the expression of a specific counter-regulatory molecule to ensure appropriate termination of pro-inflammatory Th1 immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gene Expression
  • Gene Expression Regulation / immunology*
  • Hepatitis A Virus Cellular Receptor 2
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT4 Transcription Factor / immunology
  • STAT4 Transcription Factor / metabolism
  • T-Box Domain Proteins / immunology*
  • T-Box Domain Proteins / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology*


  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Receptors, Virus
  • STAT4 Transcription Factor
  • T-Box Domain Proteins
  • T-box transcription factor TBX21