Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
| Autor: | Mohamed Rachid Boulassel, Elias K. Haddad, Robert Balderas, Elias A. Said, Eric Delwart, Lydie Trautmann, Sylvain Gimmig, Homero Sepulveda, Benoit Bessette, Rafick Pierre Sekaly, Jean-Pierre Routy, Nicolas Chomont, Loury Janbazian |
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| Rok vydání: | 2006 |
| Předmět: |
CD3 Complex
Molecular Sequence Data Programmed Cell Death 1 Receptor Receptors Antigen T-Cell HIV Infections CD8-Positive T-Lymphocytes Biology General Biochemistry Genetics and Molecular Biology CCL5 Immunophenotyping Interleukin 21 Antigen Antigens CD Humans Cytotoxic T cell Amino Acid Sequence IL-2 receptor Antigen-presenting cell Cell Proliferation ZAP70 Cell Differentiation General Medicine Up-Regulation Cell biology Immune System Diseases Immune System Cytokines Apoptosis Regulatory Proteins CD8 |
| Zdroj: | Nature Medicine. 12:1198-1202 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L21,2,3,4, 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 load8. During chronic HIV infection, HIV-specific CD8+ T cells are functionally impaired9,10,11, showing a reduced capacity to produce cytokines and effector molecules as well as an impaired capacity to proliferate12,13,14,15. 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. |
| Databáze: | OpenAIRE |
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