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

J Exp Med. 2018 Mar 5;215(3):773-783. doi: 10.1084/jem.20171584. Epub 2018 Feb 12.

Abstract

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 KLRG1hi CD8+ T cell population after lymphocytic choriomeningitis virus infection. Induced deletion of Id2 phenotypically and transcriptionally transformed the KLRG1hi "terminal" effector/effector-memory CD8+ T cell population into a KLRG1lo memory-like population, promoting a gene-expression program that resembled that of central memory T cells. Our results question the idea that KLRG1hi CD8+ T cells are necessarily terminally programmed and suggest that sustained regulation is required to maintain distinct CD8+ T cell states.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation*
  • Gene Deletion
  • Inhibitor of Differentiation Protein 2 / metabolism*
  • Lectins, C-Type
  • Mice, Inbred C57BL
  • Protein Binding
  • Receptors, Immunologic / metabolism

Substances

  • Antigens
  • Basic Helix-Loop-Helix Transcription Factors
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Tcf3 protein, mouse