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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Nature, Volume 443, No. 7109, Year 2006
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Description
Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. © 2006 Nature Publishing Group.
Authors & Co-Authors
Day, Cheryl Cheryl L.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
United Kingdom, Oxford
Nuffield Department of Medicine
Kaufmann, Daniel Elias
United States, Boston
Massachusetts General Hospital
Kiepiela, Photini
South Africa, Durban
University of Kwazulu-natal
Brown, Julia A.
United States, Boston
Harvard Medical School
Moodley, Eshia S.
South Africa, Durban
University of Kwazulu-natal
Reddy, Sharon
South Africa, Durban
University of Kwazulu-natal
Mackey, Elizabeth W.
United States, Boston
Massachusetts General Hospital
Miller, Joseph D.
United States, Atlanta
Emory University School of Medicine
Leslie, Alasdair J.
United Kingdom, Oxford
Nuffield Department of Medicine
DePierres, Chantal
South Africa, Durban
University of Kwazulu-natal
Mncube, Zenele
South Africa, Durban
University of Kwazulu-natal
Duraiswamy, Jaikumar
United States, Atlanta
Emory University School of Medicine
Zhu, Baogong
United States, Boston
Harvard Medical School
Eichbaum, Quentin G.
United States, Boston
Massachusetts General Hospital
Altfeld, Marcus A.
United States, Boston
Massachusetts General Hospital
Wherry, Edward John
United States, Philadelphia
The Wistar Institute
Coovadia, Hoosen Mahomed
South Africa, Durban
University of Kwazulu-natal
Goulder, Philip Jeremy Renshaw
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
United Kingdom, Oxford
Nuffield Department of Medicine
Klenerman, Paul
United Kingdom, Oxford
Nuffield Department of Medicine
Ahmed, Rafi S.
United States, Atlanta
Emory University School of Medicine
Freeman, Gordon James
United States, Boston
Harvard Medical School
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 2,707
Authors: 22
Affiliations: 7
Identifiers
Doi:
10.1038/nature05115
ISSN:
00280836
e-ISSN:
14764687
Research Areas
Infectious Diseases