title: The PD-1/PD-L1 (B7-H1) pathway in chronic infection-induced cytotoxic T lymphocyte exhaustion.
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.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Hofmeyer
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Jeon
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D006801:Humans; D007239:Infections / Q000276:immunology* / Q000382:microbiology; D008099:Liver / Q000276:immunology / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D018106:CD28 Antigens; D061026:Programmed Cell Death 1 Receptor