Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1.
Details
Serval ID
serval:BIB_DA3B91B63632
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1.
Journal
Journal of immunology
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
01/01/2010
Peer-reviewed
Oui
Volume
184
Number
1
Pages
476-487
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Ongoing antigenic stimulation appears to be an important prerequisite for the persistent expression of programmed death 1 (PD-1), an inhibitory TCR coreceptor of the CD28 family. Although recent publications have emphasized the utility of PD-1 as a marker for dysfunctional T cells in chronic viral infections, its dependence on antigenic stimulation potentially renders it a sensitive indicator of low-level viral replication. To explore the antigenic threshold for the maintenance of PD-1 expression on virus-specific T cells, we compared PD-1 expression on virus-specific and memory T cell populations in controlled and uncontrolled SIV and HIV-1 infection. In both controlled live attenuated SIV infection in rhesus macaques and HIV-1 infection in elite controllers, elevated levels of PD-1 expression were observed on SIV- and HIV-1-specific CD8(+) T cells. However, in contrast to chronic wild-type SIV infection and uncontrolled HIV-1 infection, controlled SIV/HIV-1 infection did not result in increased expression of PD-1 on total memory T cells. PD-1 expression on SIV-specific CD8(+) T cells rapidly decreased after the emergence of CTL escape in cognate epitopes, but was maintained in the setting of low or undetectable levels of plasma viremia in live attenuated SIV-infected macaques. After inoculation of naive macaques with a single-cycle SIV, PD-1 expression on SIV-specific CD8(+) T cells initially increased, but was rapidly downregulated. These results demonstrate that PD-1 can serve as a sensitive indicator of persistent, low-level virus replication and that generalized PD-1 expression on T lymphocytes is a distinguishing characteristic of uncontrolled lentiviral infections.
Keywords
Animals, Antigens, CD/biosynthesis, Antigens, CD/immunology, Apoptosis Regulatory Proteins/biosynthesis, Apoptosis Regulatory Proteins/immunology, Biomarkers/analysis, Flow Cytometry, HIV Infections/immunology, HIV Infections/metabolism, HIV-1/immunology, Humans, Macaca mulatta, Programmed Cell Death 1 Receptor, Reverse Transcriptase Polymerase Chain Reaction, Simian Acquired Immunodeficiency Syndrome/immunology, Simian Acquired Immunodeficiency Syndrome/metabolism, Simian Immunodeficiency Virus/immunology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, T-Lymphocytes/virology, Viremia, Virus Replication/immunology
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Create date
09/05/2023 13:00
Last modification date
29/11/2024 17:12