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

Lydie Trautmann, Elias A. Said, Rabih Halwani, Loury Janbazian, Nicolas Chomont, Mohamed El-Far, Gaëlle Breton, Elias K. Haddad, Rafick Pierre Sekaly

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16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalCurrent Opinion in HIV and AIDS
Volume2
Issue number3
DOIs
Publication statusPublished - May 2007

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Keywords

  • Autoimmunity
  • Cancer
  • Chronic viral infections
  • Immunotherapy
  • Programmed death 1

ASJC Scopus subject areas

  • Hematology
  • Oncology(nursing)
  • Immunology
  • Infectious Diseases
  • Virology
  • Oncology

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