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

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.