Reviving exhausted T lymphocytes during chronic virus infection by B7-H1 blockade.
Cytotoxic T lymphocytes (CTLs) are killer cells that are crucial in the control of viral pathogens and cancers. They can become exhausted during chronic viral infection, a phenomenon that consists of a reduction in both number and functionality of CTLs. Recently, Barber and colleagues demonstrated that B7-H1 (also called PD-L1), a cell-surface molecule that is widely distributed in tissues, was necessary for the maintenance of T-cell exhaustion in a chronic-infection mouse model of lymphocytic choriomeningitis virus (LCMV). PD-1, the receptor of B7-H1, was greatly upregulated on CTLs in response to LCMV, and its expression was maintained during chronic infection. Blockade of the B7-H1-PD-1 pathway by a monoclonal antibody restored CTL function and reduced viral burden. These results suggest a new strategy for the treatment of chronic viral infection.
Yao
Sheng
S
Department of Dermatology, and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Chen
Lieping
L
D000818:Animals; D000906:Antibodies; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002908:Chronic Disease; D005786:Gene Expression Regulation; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor
D000906:Antibodies; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor