Journal
OPEN BIOLOGY
Volume 6, Issue 1, Pages -Publisher
ROYAL SOC
DOI: 10.1098/rsob.150208
Keywords
c-Myc; costimulation; CD8(+) T cells; memory; viral infection
Categories
Funding
- National Institute of Health [R21AI109239, K18CA151798]
- Leona M. and Harry B. Helmsley Charitable Trust [2014PG-T1D049]
- Pennsylvania Department of Health using Tobacco Settlement Funds
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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 Cd282/2 or Ox402/2 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 downstreammolecule of NF-kappa B 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.
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