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.