Human Gene Set: GSE40666_NAIVE_VS_EFFECTOR_CD8_TCELL_WITH_IFNA_STIM_90MIN_DN


Standard name GSE40666_NAIVE_VS_EFFECTOR_CD8_TCELL_WITH_IFNA_STIM_90MIN_DN
Systematic name M9211
Brief description Genes down-regulated in CD8 T cells treated by interferon alpha: naïve versus day 8 after LCMV infection.
Full description or abstract Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 as compared to STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22968462   Authors: Gil MP,Ploquin MJ,Watford WT,Lee SH,Kim K,Wang X,Kanno Y,O'Shea JJ,Biron CA
Exact source GSE40666_3511_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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