Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory

PLoS Pathog. 2017 Aug 21;13(8):e1006544. doi: 10.1371/journal.ppat.1006544. eCollection 2017 Aug.


Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8+ T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32-/- mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8+ T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8+ effector T cells that is required for the balanced regulation of effector versus memory responses to infection.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Arenaviridae Infections / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Chromatin Immunoprecipitation
  • Disease Models, Animal
  • Flow Cytometry
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Polymerase Chain Reaction
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / immunology*


  • Repressor Proteins
  • Rog protein, mouse