Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection

Peiyuan Lu, Benjamin A. Youngblood, James J. Austin, Ata Ur Rasheed Mohammed, Royce Butler, Rafi Ahmed, Jeremy M. Boss

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Programmed cell death 1 (PD-1) is an inhibitory immune receptor that regulates T cell function, yet the molecular events that control its expression are largely unknown. We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1.

Original languageEnglish (US)
Pages (from-to)515-527
Number of pages13
JournalJournal of Experimental Medicine
Volume211
Issue number3
DOIs
StatePublished - Mar 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lu, P., Youngblood, B. A., Austin, J. J., Mohammed, A. U. R., Butler, R., Ahmed, R., & Boss, J. M. (2014). Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. Journal of Experimental Medicine, 211(3), 515-527. https://doi.org/10.1084/jem.20130208