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Programmed death 1: a critical regulator of T-cell function and a strong target for immunotherapies for chronic viral infections

Trautmann, Lydiea,b,c; Said, Elias Aa,b,c; Halwani, Rabiha,b,c; Janbazian, Lourya,d; Chomont, Nicolasa,b,c; El-Far, Mohameda,b,c; Breton, Gaëllea,b,c; Haddad, Elias Ka,b,c,d; Sekaly, Rafick-Pierreabcd

Current Opinion in HIV and AIDS: May 2007 - Volume 2 - Issue 3 - p 219–227
doi: 10.1097/COH.0b013e3280ebb5c9
Immunological monitoring and immunotherapy: Clinical science
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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.

aLaboratoire d'Immunologie, Centre de Recherche CHUM Saint-Luc, Montréal, Québec, Canada

bLaboratoire d'Immunologie, Département de Microbiologie et d'Immunologie, Université de Montréal, Québec, Canada

cINSERM U743, CR-CHUM, Université de Montréal, Montréal, Québec, Canada

dDepartment of Microbiology and Immunology, McGill University, Montréal, Québec, Canada

Correspondence to Rafick-Pierre Sékaly, Department of Microbiology and Immunology, Centre de Recherche Campus St. Luc, Pavillon Edouard-Asselin, 264 rue Rene Levesque Est., Bureau 1307E, Montreal, QC H2X 1P1, Canada Tel: +1 514 8908000 (ext. 35288); fax: +1 514 4127415; e-mail: rafick-pierre.sekaly@umontreal.ca

Sponsorship: This work was supported by grants awarded to R.P.S. from the National Institutes of Health, the Canadian Institutes of Health Research, the Canadian Network for Vaccine and Immunotherapeutics, Genome Quebec, Genome Canada and Valorisation Recherche Québec. R.P.S. is the Canada Research Chair in Human Immunology.

© 2007 Lippincott Williams & Wilkins, Inc.