Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade.
The programmed death (PD)-1-PD-1 ligand (PD-L) pathway, which is part of the B7-CD28 family, consists of the PD-1 receptor and its two ligands PD-L1 and PD-L2. Engagement of PD-1 by its ligands inhibits immune responses, and recent work has shown that PD-1 is highly expressed on exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Blockade of this pathway reinvigorates the exhausted T cells, allowing them to expand and produce effector cytokines, raising the issue of whether this pathway has been exploited by a variety of viruses during chronic infection. New studies now extend these observations to HIV infection and human disease.
Freeman
Gordon J
GJ
Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. gordon_freeman@dfci.harvard.edu
Wherry
E John
EJ
Ahmed
Rafi
R
Sharpe
Arlene H
AH
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D008024:Ligands; D008217:Lymphocytic choriomeningitis virus; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D010455:Peptides