The PD-1/PD-L1 (B7-H1) pathway in chronic infection-induced cytotoxic T lymphocyte exhaustion

J Biomed Biotechnol. 2011;2011:451694. doi: 10.1155/2011/451694. Epub 2011 Sep 25.

Abstract

Cytotoxic CD8 T lymphocytes (CTLs) play a pivotal role in the control of infection. Activated CTLs, however, often lose effector function during chronic infection. PD-1 receptor and its ligand PD-L1 of the B7/CD28 family function as a T cell coinhibitory pathway and are emerging as major regulators converting effector CTLs into exhausted CTLs during chronic infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and other pathogens capable of establishing chronic infections. Importantly, blockade of the PD-1/PD-L1 pathway is able to restore functional capabilities to exhausted CTLs and early clinical trials have shown promise. Further research will reveal how chronic infection induces upregulation of PD-1 on CTLs and PD-L1 on antigen-presenting cells and other tissue cells and how the PD-1/PD-L1 interaction promotes CTLs exhaustion, which is crucial for developing effective prophylactic and therapeutic vaccination against chronic infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • CD28 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Chronic Disease
  • Humans
  • Infections / immunology*
  • Infections / microbiology
  • Liver / immunology
  • Liver / metabolism
  • Metabolic Networks and Pathways
  • Mice
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • B7-H1 Antigen
  • CD28 Antigens
  • Programmed Cell Death 1 Receptor