PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression

Cheryl L. Day, Daniel E. Kaufmann, Photini Kiepiela, Julia A. Brown, Eshia S. Moodley, Sharon Reddy, Elizabeth W. Mackey, Joseph D. Miller, Alasdair J. Leslie, Chantal DePierres, Zenele Mncube, Jaikumar Duraiswamy, Baogong Zhu, Quentin Eichbaum, Marcus Altfeld, E. John Wherry, Hoosen M. Coovadia, Philip J. R. Goulder, Paul Klenerman, Rafi Ahmed, Gordon J. Freeman and Bruce D. Walker ()
Additional contact information
Cheryl L. Day: Doris Duke Medical Research Institute, University of KwaZulu Natal
Daniel E. Kaufmann: Massachusetts General Hospital and Division of AIDS, Harvard Medical School
Photini Kiepiela: Doris Duke Medical Research Institute, University of KwaZulu Natal
Julia A. Brown: Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School
Eshia S. Moodley: Doris Duke Medical Research Institute, University of KwaZulu Natal
Sharon Reddy: Doris Duke Medical Research Institute, University of KwaZulu Natal
Elizabeth W. Mackey: Massachusetts General Hospital and Division of AIDS, Harvard Medical School
Joseph D. Miller: Emory University School of Medicine
Alasdair J. Leslie: The Peter Medawar Building for Pathogen Research, Oxford University
Chantal DePierres: Doris Duke Medical Research Institute, University of KwaZulu Natal
Zenele Mncube: Doris Duke Medical Research Institute, University of KwaZulu Natal
Jaikumar Duraiswamy: Emory University School of Medicine
Baogong Zhu: Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School
Quentin Eichbaum: Massachusetts General Hospital and Division of AIDS, Harvard Medical School
Marcus Altfeld: Massachusetts General Hospital and Division of AIDS, Harvard Medical School
E. John Wherry: The Wistar Institute
Hoosen M. Coovadia: Doris Duke Medical Research Institute, University of KwaZulu Natal
Philip J. R. Goulder: Doris Duke Medical Research Institute, University of KwaZulu Natal
Paul Klenerman: The Peter Medawar Building for Pathogen Research, Oxford University
Rafi Ahmed: Emory University School of Medicine
Gordon J. Freeman: Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School
Bruce D. Walker: Doris Duke Medical Research Institute, University of KwaZulu Natal

Nature, 2006, vol. 443, issue 7109, 350-354

Abstract: HIV and immunity Blocking a protein called PD-1 (programmed death 1) might provide a way to boost the immune function of T cells crippled by HIV infection. A study published earlier this year showed that blocking of PD-1 function in virally infected mice could restore the function of exhausted T cells and help fight infection. Now the phenomenon has been found to occur in humans. The T cells in HIV patients were found to have many more PD-1 receptors on their surface than is normal; the degree of PD-1 production correlates with markers of disease progression including the extent to which T cells are disabled and the levels of virus within the body. An antibody that blocks this receptor promotes the immune response to HIV in laboratory experiments, suggesting that a similar strategy might work to fight the disease in humans.

Date: 2006
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DOI: 10.1038/nature05115

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