The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4+ T cells

Immunity. 2008 Dec 19;29(6):876-87. doi: 10.1016/j.immuni.2008.09.019. Epub 2008 Dec 8.


How CD4-CD8 differentiation is maintained in mature T cells is largely unknown. The present study has examined the role in this process of the zinc finger protein Zbtb7b, a critical factor for the commitment of MHC II-restricted thymocytes to the CD4+ lineage. We showed that Zbtb7b acted in peripheral CD4+ T cells to suppress CD8-lineage gene expression, including that of CD8 and cytotoxic effector genes perforin and Granzyme B, and was important for the proper repression of interferon-gamma (IFN-gamma) during effector differentiation. The inappropriate expression of IFN-gamma by Zbtb7b-deficient CD4+ T cells required the activities of Eomesodermin and Runx transcription factors. Runx activity was needed for Granzyme B expression, indicating that Runx proteins control expression of the cytotoxic program. We conclude that a key function of Zbtb7b in the mature CD4+ T cell compartment is to repress CD8-lineage gene expression.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Lineage / genetics*
  • Cell Lineage / immunology
  • Core Binding Factor Alpha 3 Subunit / immunology
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / immunology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*


  • Core Binding Factor Alpha 3 Subunit
  • DNA-Binding Proteins
  • Runx3 protein, mouse
  • Transcription Factors
  • Zbtb7b protein, mouse