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
Title
Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1.
Journal
Journal of immunology
Author(s)
Salisch N.C., Kaufmann D.E., Awad A.S., Reeves R.K., Tighe D.P., Li Y., Piatak M., Lifson J.D., Evans D.T., Pereyra F., Freeman G.J., Johnson R.P.
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
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
Pubmed
Web of science
Create date
09/05/2023 13:00
Last modification date
29/11/2024 17:12
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