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

Abstract:

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.

journal_name

Curr Opin HIV AIDS

authors

Trautmann L,Said EA,Halwani R,Janbazian L,Chomont N,El-Far M,Breton G,Haddad EK,Sekaly RP

doi

10.1097/COH.0b013e3280ebb5c9

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

219-27

issue

3

eissn

1746-630X

issn

1746-6318

pii

01222929-200705000-00009

journal_volume

2

pub_type

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