title: Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection.
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.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Lu
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Youngblood
authors.forename: James W
authors.initials: JW
authors.lastname: Austin
authors.forename: Ata Ur Rasheed
authors.initials: AU
authors.lastname: Mohammed
authors.forename: Royce
authors.initials: R
authors.lastname: Butler
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Boss
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D008156:Luciferases; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D017931:DNA Primers; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C491383:Pdcd1 protein, mouse; C513258:Prdm1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D014157:Transcription Factors; D008156:Luciferases; D000074462:Positive Regulatory Domain I-Binding Factor 1