Human Gene Set: GSE14699_DELETIONAL_TOLERANCE_VS_ACTIVATED_CD8_TCELL_DN


Standard name GSE14699_DELETIONAL_TOLERANCE_VS_ACTIVATED_CD8_TCELL_DN
Systematic name M2939
Brief description Genes down-regulated in CD8 T cells: undergoing deletional tolerance versus activated.
Full description or abstract Peripheral tolerance induction is critical for the maintenance of self-tolerance and can be mediated by immunoregulatory T cells or by direct induction of T cell anergy or deletion. While the molecular processes underlying anergy have been extensively studied, little is known about the molecular basis for peripheral T cell deletion. Here, we determined the gene expression signature of peripheral CD8+ T cells undergoing deletional tolerance, relative to those undergoing immunogenic priming or lymphopenia-induced proliferation. From these data, we report the first detailed molecular signature of cells undergoing deletion. Consistent with defective cytolysis, these cells exhibited deficiencies in granzyme up-regulation. Furthermore, they showed antigen-driven Bcl-2 down-regulation and early up-regulation of the pro-apoptotic protein Bim, consistent with the requirement of this BH3-only protein for peripheral T cell deletion. Bim up-regulation was paralleled by defective IL-7Ra chain re-expression, suggesting that Bim-dependent death may be triggered by loss of IL-7/IL-7R signaling. Finally, we observed parallels in molecular signatures between deletion and anergy suggesting that these tolerance pathways may not be as molecularly distinct as previously surmised.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19204323   Authors: Parish IA,Rao S,Smyth GK,Juelich T,Denyer GS,Davey GM,Strasser A,Heath WR
Exact source GSE14699_3152_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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