Transcriptional modulation of TCR, Notch and Wnt signaling pathways in SEB-anergized CD4+ T cells

Genes Immun. 2005 Oct;6(7):596-608. doi: 10.1038/sj.gene.6364245.


Gene expression changes in CD4 + Vbeta8+ T cells energized by in vivo exposure to staphylococcal enterotoxin B (SEB) bacterial superantigen compared to CD4 + Vbeta8+ non-energic T cells were assessed using DNA microarrays containing 5184 murine complementary DNAs. Anergy in splenic T cells of SEB-immunized BALB/c mice was verified by dramatically reduced proliferative capacity and an 8 x overexpression of GRAIL mRNA in CD4 + Vbeta8+ T cells taken from mice 7 days after injection. At an Associative t-test threshold of P<0.0005, 96 genes were overexpressed or detected only in anergic T cells, while 256 genes were suppressed or not detected in anergic T cells. Six of eight differential expressions tested using real-time quantitative PCR were validated. Message for B-Raf was detected only in non-anergic cells, while expression of the TCR signaling modulator Slap (Src-like adapter protein) and the TCR zeta-chain specific phosphatase Ptpn3 was enhanced. Modulation of multiple genes suggests downregulation of Wnt/beta-catenin signaling and enhanced Notch signaling in the anergic cells. Consistent with previous reports in a non-superantigen in vivo anergy model, mRNA for CD18 and the transcription factor Satb1 (special AT-rich-binding protein 1) was increased in SEB-energized T cells. This is the first report of global transcriptional changes in CD4+ T cells made anergic by superantigen exposure.

Publication types

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

MeSH terms

  • Animals
  • CD18 Antigens / genetics
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Cycle / genetics
  • Cell Proliferation
  • Clonal Anergy / genetics*
  • Enterotoxins / immunology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Matrix Attachment Region Binding Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Notch / genetics
  • Signal Transduction / genetics*
  • Spleen / immunology
  • Superantigens / immunology*
  • Transcription, Genetic
  • Wnt Proteins / genetics


  • CD18 Antigens
  • Enterotoxins
  • Matrix Attachment Region Binding Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Notch
  • Satb1 protein, mouse
  • Superantigens
  • Wnt Proteins
  • enterotoxin B, staphylococcal