Transcriptional modulation of TCR, Notch and Wnt signaling pathways in SEB-anergized CD4+ T cells.
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.
Kurella
S
S
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Yaciuk
J C
JC
Dozmorov
I
I
Frank
M B
MB
Centola
M
M
Farris
A D
AD
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D017635:Clonal Anergy / Q000235:genetics*; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000235:genetics
D018821:CD18 Antigens; D004768:Enterotoxins; D036961:Matrix Attachment Region Binding Proteins; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; C469541:Satb1 protein, mouse; D018089:Superantigens; D051153:Wnt Proteins; C031818:enterotoxin B, staphylococcal