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

S. Kurella, J. C. Yaciuk, I. Dozmorov, M. B. Frank, M. Centola, A. D. Farris

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Gene expression changes in CD4 + Vβ8+ T cells anergized by in vivo exposure to staphylococcal enterotoxin B (SEB) bacterial superantigen compared to CD4 + Vβ8+ nonanergic 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 × overexpression of GRAIL mRNA in CD4 + Vβ8+ 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 ζ-chain specific phosphatase Ptpn3 was enhanced. Modulation of multiple genes suggests downregulation of Wnt/β-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-anergized T cells. This is the first report of global transcriptional changes in CD4+ T cells made anergic by superantigen exposure.

Original languageEnglish (US)
Pages (from-to)596-608
Number of pages13
JournalGenes and Immunity
Volume6
Issue number7
DOIs
StatePublished - Oct 1 2005

Keywords

  • Anergy
  • Microarray
  • Rodent
  • Superantigen
  • T cell

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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