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Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo

Research output: Contribution to journalArticlepeer-review

Author(s)

MP Gil, R Salomon, J Louten, CA Biron

School/Research organisations

Abstract

Type 1 interferons (IFNs) are induced in vivo, administered therapeutically, and potential targets for amelioration of autoimmune diseases. The cytokines mediate profound antiproliferative effects. Signal transducer and activator of transcription 1 (STAT1)-dependent signaling pathways are required for inhibition of proliferation, and viral infections can elicit high levels of type 1 IFNs as well as total STAT1 protein expression. Thus, a mechanism must be in place to help antigen-specific T cells overcome IFN-induced inhibition of proliferation. The studies reported here demonstrate that total CD8 T-cell proliferation in the presence of IFNs, ex vivo in response to cytokines and in vivo during viral infection, is inhibited through a STAT1-dependent mechanism. In contrast, major proportions of antigen-specific CD8, but not CD4, T cells are rendered less sensitive to this inhibition, express lower endogenous levels of total STAT1, and are selectively proliferating in the of type 1 IFN, at key times after viral challenge. Taken together, these novel results show that differential STAT1 expression is used by the immune system to modify cytokine-mediated effects on T-cell expansion and have implications for the consequences of therapeutic intervention in cytokine function.

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Details

Original languageEnglish
Pages (from-to)987-993
Number of pages7
JournalBlood
Volume107
Issue number3
DOIs
Publication statusPublished - 1 Feb 2006

    Research areas

  • LYMPHOCYTIC CHORIOMENINGITIS VIRUS, IFN-ALPHA-BETA, INTERFERON-GAMMA, VIRAL-INFECTION, INDEPENDENT PATHWAYS, FLOW-CYTOMETRY, CUTTING EDGE, ACTIVATION, INDUCTION, EXPANSION

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