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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 451694, 9 pages
http://dx.doi.org/10.1155/2011/451694
Review Article

The PD-1/PD-L1 (B7-H1) Pathway in Chronic Infection-Induced Cytotoxic T Lymphocyte Exhaustion

1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
4Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
5Einstein-Montefiore Center for AIDS Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Received 1 July 2011; Accepted 21 July 2011

Academic Editor: Julie Curtsinger

Copyright © 2011 Kimberly A. Hofmeyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.