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 language | English (US) |
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Pages (from-to) | 596-608 |
Number of pages | 13 |
Journal | Genes and Immunity |
Volume | 6 |
Issue number | 7 |
DOIs | |
State | Published - Oct 2005 |
Keywords
- Anergy
- Microarray
- Rodent
- Superantigen
- T cell
ASJC Scopus subject areas
- Immunology
- Genetics
- Genetics(clinical)