Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits CD8(+) T cell memory formation

Blimp-1 is a transcriptional repressor that promotes the differentiation of CD8(+) T cells into short-lived KLRG-1(+) effector cells (SLEC), but how it operates remains poorly defined. Here we show that Blimp-1 binds and represses the Id3 promoter in SLEC. Repression of Id3 by Blimp-1 was dispensable for SLEC development but limited their capacity to persist as memory cells. Enforced expression of Id3 was sufficient to rescue SLEC survival and enhanced recall responses. Id3 function was mediated in part through inhibition of E2a transcriptional activity and induction of genes regulating genome stability. These findings identify a Blimp-1-Id3-E2a axis as a key molecular switch that determines whether effector CD8(+) T cells are programmed to die or enter the memory pool.