Sustained Id2 regulation of E proteins is required for terminal differentiation of effector CD8(+) T cells

CD8(+) T cells responding to infection differentiate into a heterogeneous population composed of progeny that are short-lived and participate in the immediate, acute response and those that provide long-lasting host protection. Although it is appreciated that distinct functional and phenotypic CD8(+) T cell subsets persist, it is unclear whether there is plasticity among subsets and what mechanisms maintain subset-specific differences. Here, we show that continued Id2 regulation of E-protein activity is required to maintain the KLRG1(hi) CD8(+) T cell population after lymphocytic choriomeningitis virus infection. Induced deletion of Id2 phenotypically and transcriptionally transformed the KLRG1(hi) “terminal” effector/effector-memory CD8(+) T cell population into a KLRG1(lo) memory-like population, promoting a gene-expression program that resembled that of central memory T cells. Our results question the idea that KLRG1(hi) CD8(+) T cells are necessarily terminally programmed and suggest that sustained regulation is required to maintain distinct CD8(+) T cell states.