PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on...
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| Published in | The Journal of experimental medicine Vol. 203; no. 10; pp. 2281 - 2292 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
The Rockefeller University Press
02.10.2006
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
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| AbstractList | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8
+
T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8
+
T cells and increased on memory CD8
+
T cells according to antigen specificity. Memory CD8
+
T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8
+
T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8
+
T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8
+
T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8
+
T cell numbers, but possibly not all functions in vivo. Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| Author | Petrovas, Constantinos Douek, Daniel C Gostick, Emma Schacker, Timothy Adams, William C Casazza, Joseph P Koup, Richard A Brenchley, Jason M Price, David A Precopio, Melissa L Roederer, Mario |
| AuthorAffiliation | 3 Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK 4 Department of Medicine, University of Minnesota, Minneapolis, MN 55455 1 Immunology Laboratory, 2 Human Immunology Section, and 5 ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 |
| AuthorAffiliation_xml | – name: 4 Department of Medicine, University of Minnesota, Minneapolis, MN 55455 – name: 3 Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK – name: 1 Immunology Laboratory, 2 Human Immunology Section, and 5 ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 |
| Author_xml | – sequence: 1 givenname: Constantinos surname: Petrovas fullname: Petrovas, Constantinos organization: Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 2 givenname: Joseph P surname: Casazza fullname: Casazza, Joseph P – sequence: 3 givenname: Jason M surname: Brenchley fullname: Brenchley, Jason M – sequence: 4 givenname: David A surname: Price fullname: Price, David A – sequence: 5 givenname: Emma surname: Gostick fullname: Gostick, Emma – sequence: 6 givenname: William C surname: Adams fullname: Adams, William C – sequence: 7 givenname: Melissa L surname: Precopio fullname: Precopio, Melissa L – sequence: 8 givenname: Timothy surname: Schacker fullname: Schacker, Timothy – sequence: 9 givenname: Mario surname: Roederer fullname: Roederer, Mario – sequence: 10 givenname: Daniel C surname: Douek fullname: Douek, Daniel C – sequence: 11 givenname: Richard A surname: Koup fullname: Koup, Richard A |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16954372$$D View this record in MEDLINE/PubMed |
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| License | This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 CORRESPONDENCE Richard A. Koup: rkoup@mail.nih.gov Abbreviations used: mDC, myeloid dendritic cell; PD, programmed death; pDC, plasmacytoid dendritic cell; PD-L, programmed death ligand; TLR, toll-like receptor; VV, vaccinia virus. |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118095/ |
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| PublicationTitle | The Journal of experimental medicine |
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| Publisher | The Rockefeller University Press |
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| Snippet | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on... Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8+ T cells and the effect of manipulating signaling through PD-1 on the... Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8 + T cells and the effect of manipulating signaling through PD-1 on the... |
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| SubjectTerms | Antigens, CD - immunology Antigens, CD - metabolism Apoptosis - immunology Apoptosis Regulatory Proteins - immunology Apoptosis Regulatory Proteins - metabolism CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology Cell Survival Flow Cytometry HIV Infections - immunology Humans Programmed Cell Death 1 Receptor |
| Title | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection |
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