C-Myc regulation by costimulatory signals modulates the generation of CD8+ memory T cells during viral infection

Jianxun Song*, Mohammad Haque, Jianyong Song, Kristin Fino, Youfei Wang, Praneet Sandhu, Xinmeng Song, Christopher Norbury, Bing Ni, Deyu Fang, Shahram Salek-Ardakani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8+ T cells is controlled by costimulatory molecules, which modulates the development of memory CD8+ T cells. C-Myc expression was dramatically reduced in Cd28-/- or Ox40-/- memory CD8+ T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8+ T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF-κB and intracellular target of costimulation that controls survival, in Cd28-/- or Ox40-/- CD8+ T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8+ T cells from costimulatory signals.

Original languageEnglish (US)
Article number150208
JournalOpen Biology
Volume6
Issue number1
DOIs
StatePublished - Jan 2016

Keywords

  • C-MyC
  • CD8 T cells
  • Costimulation
  • Memory
  • Viral infection

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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