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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Arenaviridae Infections / immunology*
-
Binding Sites / genetics
-
CD8-Positive T-Lymphocytes / metabolism*
-
Cell Line, Tumor
-
Chromatin Immunoprecipitation
-
DNA Primers / genetics
-
Gene Expression Regulation / immunology*
-
Luciferases
-
Lymphocytic choriomeningitis virus / immunology*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
NFATC Transcription Factors / metabolism
-
Positive Regulatory Domain I-Binding Factor 1
-
Programmed Cell Death 1 Receptor / metabolism*
-
Real-Time Polymerase Chain Reaction
-
Reverse Transcriptase Polymerase Chain Reaction
-
Transcription Factors / deficiency
-
Transcription Factors / genetics
-
Transcription Factors / immunology*
Substances
-
DNA Primers
-
NFATC Transcription Factors
-
Nfatc1 protein, mouse
-
Pdcd1 protein, mouse
-
Prdm1 protein, mouse
-
Programmed Cell Death 1 Receptor
-
Transcription Factors
-
Luciferases
-
Positive Regulatory Domain I-Binding Factor 1