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

Open Biol. 2016 Jan;6(1):150208. doi: 10.1098/rsob.150208.

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.

Keywords: CD8+ T cells; c-Myc; costimulation; memory; viral infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD28 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Gene Expression Regulation
  • I-kappa B Kinase / metabolism
  • Immunity
  • Immunologic Memory* / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Receptors, OX40
  • Repressor Proteins / metabolism
  • Signal Transduction*
  • Survivin
  • Transcription, Genetic
  • Virus Diseases / immunology*
  • bcl-X Protein / metabolism

Substances

  • Birc5 protein, mouse
  • CD28 Antigens
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-myc
  • Receptors, OX40
  • Repressor Proteins
  • Survivin
  • Tnfrsf4 protein, mouse
  • bcl-X Protein
  • I-kappa B Kinase