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Cited by 1,565HIV Research and TreatmentT-cell and B-cell ImmunologyCancer Immunotherapy and Biomarkers

Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction

Trautmann, Lydie, Janbazian, Loury, Chomont, Nicolas, Said, Elias A, Gimmig, Sylvain, Bessette, Benoit, Boulassel, Mohamed-Rachid, Delwart, Eric +5 more·2006·Nature Medicine
DOI 10.1038/nm1482
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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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Crossref · 10.1038/nm1482

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  • The view that many late-stage differentiated cells are not dysfunctional or senescent is supported by studies showing that programmed death-1 (PD-1) is expressed on very few CMV-specific cells and at low levels.

    “The view that many of these late-stage differentiated cells are not dysfunctional or senescent is supported by studies showing that the inhibitory molecule programmed death-1 (PD-1) is expressed on very few CMV-specific cells and at low levels (Petrovas et al. 2006; Trautmann et al. 2006).”

    From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Trautmann et al. 2006

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Authors
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., Routy, J.-P., Haddad, E. K., & Sekaly, R.-P.
Affiliations
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Inserm (FR)
  • McGill University Health Centre (CA)
  • Blood Systems Research Institute (US)
  • BD Biosciences (United States) (US)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2006-08-20
Volume
12
Issue
10
Pages
1198-1202
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm1482
OpenAlex
W2035852466
Cited by
1,565
References
30
Citations by year
2026: 30 · 2025: 43 · 2024: 61 · 2023: 55 · 2022: 57 · 2021: 67 · 2020: 75 · 2019: 75 · 2018: 80 · 2017: 72 · 2016: 65 · 2015: 85 · 2014: 74 · 2013: 83 · 2012: 87
FWCI
38.71
Type
journal article
Language
en
Update notices
erratum (2006-11-01)
Open access
closed
Licence
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
PD-1, HIV-specific CD8+ T cells, PD-L1, PD-L2, T cell exhaustion, chronic HIV infection, viral load, cytokine production, T cell proliferation, cytomegalovirus-specific T cells, anti-PD-1 therapy, T cell dysfunction, immune dysfunction
MeSH terms
Amino Acid Sequence, Cell Differentiation, Humans, Immune System, Immune System Diseases, Molecular Sequence Data, Receptors, Antigen, T-Cell, HIV Infections, Antigens, CD, Up-Regulation, Immunophenotyping, Cytokines, CD3 Complex, CD8-Positive T-Lymphocytes, Cell Proliferation, Apoptosis Regulatory Proteins, Programmed Cell Death 1 Receptor

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