Journal article
Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction
Nature medicine, v 12(10), pp 1198-1202
Oct 2006
PMID: 16917489
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L2, inhibits proliferation and cytokine production mediated by antibodies to CD3 (refs. 5,6,7). Blocking the PD-1-PD-L1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted CD8+ T cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load. During chronic HIV infection, HIV-specific CD8+ T cells are functionally impaired, showing a reduced capacity to produce cytokines and effector molecules as well as an impaired capacity to proliferate. Here, we found that PD-1 was upregulated on HIV-specific CD8+ T cells; PD-1 expression levels were significantly correlated both with viral load and with the reduced capacity for cytokine production and proliferation of HIV-specific CD8+ T cells. Notably, cytomegalovirus (CMV)-specific CD8+ T cells from the same donors did not upregulate PD-1 and maintained the production of high levels of cytokines. Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8+ T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen. The accumulation of HIV-specific dysfunctional CD8+ T cells in the infected host could prevent the renewal of a functionally competent HIV-specific CD8+ repertoire.
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Details
- Title
- Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction
- Creators
- Rafick-Pierre Sekaly - McGill UniversityLydie Trautmann - Centre Hospitalier de l’Université de MontréalLoury Janbazian - McGill UniversityNicolas Chomont - Université de MontréalElias A Said - Centre Hospitalier de l’Université de MontréalSylvain Gimmig - Université de MontréalBenoit Bessette - Université de MontréalMohamed-Rachid Boulassel - McGill University Health CentreEric Delwart - Blood Systems Research InstituteHomero Sepulveda - BD Biosciences (United States)Robert S Balderas - BD Biosciences (United States)Jean-Pierre Routy - McGill UniversityElias K Haddad - McGill University
- Publication Details
- Nature medicine, v 12(10), pp 1198-1202
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000241102200038
- Scopus ID
- 2-s2.0-33749009709
- Other Identifier
- 991020100078704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Medicine, Research & Experimental