Open AccessTranscriptional modulation of TCR, Notch and Wnt signaling pathways in SEB-anergized CD4+ T cells
Author(s) -
Sridevi Kurella,
Jane C. Yaciuk,
Igor Dozmorov,
M B Frank,
Michael Centola,
A. Darise Farris
Publication year - 2005
Publication title -
genes and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.35
H-Index - 100
eISSN - 1476-5470
pISSN - 1466-4879
DOI - 10.1038/sj.gene.6364245
Subject(s) - biology , wnt signaling pathway , t cell receptor , notch signaling pathway , signal transduction , microbiology and biotechnology , cancer research , genetics , t cell , immune system
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.