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J Exp Med. 2014 Mar 10;211(3):515-27. doi: 10.1084/jem.20130208. Epub 2014 Mar 3.

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

Author information

1
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.

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.

PMID:
24590765
PMCID:
PMC3949569
DOI:
10.1084/jem.20130208
[Indexed for MEDLINE]
Free PMC Article

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