title: Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells.
abstract: Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. Together, these data demonstrate that the epigenetic program at the PD-1 locus becomes fixed after prolonged exposure to HIV virus.
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Youngblood
authors.forename: Alessandra
authors.initials: A
authors.lastname: Noto
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.forename: Rama S
authors.initials: RS
authors.lastname: Akondy
authors.forename: Zaza M
authors.initials: ZM
authors.lastname: Ndhlovu
authors.forename: James W
authors.initials: JW
authors.lastname: Austin
authors.forename: Rebeka
authors.initials: R
authors.lastname: Bordi
authors.forename: Francesco A
authors.initials: FA
authors.lastname: Procopio
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Boss
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019175:DNA Methylation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D019562:Viral Load
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor