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© Michaela Muller-Trutwin
HIV
Publication : Blood

Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Blood - 11 Sep 2012

Gil MP, Ploquin MJ, Watford WT, Lee SH, Kim K, Wang X, Kanno Y, O'Shea JJ, Biron CA

Link to Pubmed [PMID] – 22968462

Blood 2012 Nov;120(18):3718-28

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 compared with 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.

http://www.ncbi.nlm.nih.gov/pubmed/22968462