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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells
Journal of Immunology, Volume 191, No. 2, Year 2013
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Description
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-1hi 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. Copyright © 2013 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Youngblood, Ben A.
United States, Atlanta
Emory University School of Medicine
Noto, Alessandra
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Porichis, Filippos
United States, Boston
Massachusetts General Hospital
Akondy, Rama S.
United States, Atlanta
Emory University School of Medicine
Ndhlovu, Zaza Mtine
United States, Boston
Massachusetts General Hospital
South Africa, Durban
The Nelson R. Mandela Medical School
Austin, James W.
United States, Atlanta
Emory University School of Medicine
Bordi, Rebeka
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Procopio, Francesco Andrea
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Miura, Toshiyuki
United Kingdom, Brentford
Viiv Healthcare
Japan, Nagasaki
Nagasaki University
Allen, Todd M.
United States, Boston
Massachusetts General Hospital
Sidney, John
United States, La Jolla
La Jolla Institute for Immunology
Sette, Alessandro D.
United States, La Jolla
La Jolla Institute for Immunology
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Ahmed, Rafi S.
United States, Atlanta
Emory University School of Medicine
Boss, Jeremy M.
United States, Atlanta
Emory University School of Medicine
Seḱaly, Rafick Pierre
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Kaufmann, Daniel Elias
United States, Boston
Massachusetts General Hospital
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
Statistics
Citations: 144
Authors: 17
Affiliations: 9
Identifiers
Doi:
10.4049/jimmunol.1203161
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Infectious Diseases