First Author | Lu P | Year | 2014 |
Journal | J Exp Med | Volume | 211 |
Issue | 3 | Pages | 515-27 |
PubMed ID | 24590765 | Mgi Jnum | J:210737 |
Mgi Id | MGI:5571778 | Doi | 10.1084/jem.20130208 |
Citation | Lu P, et al. (2014) Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. J Exp Med 211(3):515-27 |
abstractText | 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. |