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- Title
Upregulation of PD-1 expression on HIV-specific CD8<sup>+</sup> T cells leads to reversible immune dysfunction.
- Authors
Trautmann, Lydie; Janbazian, Loury; Chomont, Nicolas; Said, Elias A.; Gimmig, Sylvain; Bessette, Benoit; Boulassel, Mohamed-Rachid; Delwart, Eric; Sepulveda, Homero; Balderas, Robert S.; Routy, Jean-Pierre; Haddad, Elias K.; Sekaly, Rafick-Pierre
- 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.
- Subjects
T cells; GENE expression; HIV infections; CYTOKINES; VIRAL load; LYMPHOCYTIC choriomeningitis virus
- Publication
Nature Medicine, 2006, Vol 12, Issue 10, p1198
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1482