Journal
CURRENT OPINION IN HIV AND AIDS
Volume 2, Issue 3, Pages 219-227Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COH.0b013e3280ebb5c9
Keywords
autoimmunity; cancer; chronic viral infections; immunotherapy; programmed death 1
Categories
Funding
- National Institutes of Health
- Canadian Institutes of Health Research
- Canadian Network for Vaccine and Immunotherapeutics
- Genome Quebec
- Genome Canada
- Valorisation Recherche Quebec
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Purpose of review The intricate balance between positive and negative signals delivered by accessory molecules is crucial to generate efficient immune responses while maintaining tolerance and preventing autoimmunity. Of these molecules, programmed death 1 has been described as a negative regulator of T-cell activation. This review will focus on current knowledge about PD-1 regulation in different diseases and discuss its potential benefits for the development of novel immune therapies. Recent findings PD-1 has recently been shown to be upregulated on HIV-specific CD8 T cells, whereas the PD-1 expression level was significantly correlated with viral load. Blockade of the PD-1/PD-L1 interaction enhanced the capacity of HIV-specific CD8 and CD4 T cells to proliferate or secrete cytokines and cytotoxic molecules. Future manipulations of this pathway could rescue the function of exhausted CD8 and CD4 T cells. Summary The engagement of PD-1 with its ligands induces inhibitory signals as it blocks T-cell receptor-induced T-cell proliferation and cytokine production. The PD-1 pathway plays a crucial role in the maintenance of peripheral tolerance and the pathogenesis of cancer and chronic viral infections. Understanding the mechanisms by which PD-1 interferes with T-cell functions will pave the way for novel therapeutic immune interventions to treat these diseases.
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