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

M. Pilar Gil, Mickael J. Y. Ploquin, Wendy T. Watford, Seung-Hwan Lee, Kwangsin Kim, Xin Wang, Yuka Kanno, John J. O'Shea, Christine A. Biron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

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 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. (Blood. 2012;120(18):3718-3728)

Original languageEnglish
Pages (from-to)3718-3728
Number of pages11
JournalBlood
Volume120
Issue number18
DOIs
Publication statusPublished - 1 Nov 2012

Keywords

  • INTERFERON-GAMMA PRODUCTION
  • NATURAL-KILLER-CELLS
  • FLOW-CYTOMETRY
  • I INTERFERONS
  • RESPONSES
  • ALPHA/BETA
  • ACTIVATION
  • PATHWAYS
  • LYMPHOCYTES
  • CANCER

Fingerprint

Dive into the research topics of 'Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function'. Together they form a unique fingerprint.

Cite this