Blocking of PDL-1 Interaction Enhances Primary and Secondary CD8 T Cell Response to Herpes Simplex Virus-1 Infection

• Published in: PloS one Vol. 7; no. 7; p. e39757
• Main Authors: Channappanavar, Rudragouda, Twardy, Brandon S., Suvas, Susmit
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.07.2012; Public Library of Science (PLoS)
• Subjects: Acute Disease; Animals; Antibodies, Monoclonal - pharmacology; Antigens; Apoptosis; Assaying; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Bacterial infections; Biology; CD11c antigen; CD11c Antigen - genetics; CD11c Antigen - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cytokines; Cytotoxicity; Degranulation; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - virology; Female; Gene Expression - immunology; Health aspects; Herpes simplex; Herpes Simplex - drug therapy; Herpes Simplex - immunology; Herpes Simplex - virology; Herpes simplex virus; Herpes viruses; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - physiology; Humans; Immunization; Immunoassay; Immunodominant Epitopes - administration & dosage; Immunodominant Epitopes - genetics; Immunodominant Epitopes - immunology; Immunologic Memory - drug effects; Immunological memory; Infection; Infections; Injections, Intraperitoneal; Injections, Subcutaneous; Ligands; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Oligopeptides - administration & dosage; Oligopeptides - genetics; Oligopeptides - immunology; PD-1 protein; Peptides; Priming; Spleen; T cell receptors; T cells; Toxicity; Vaccines; Viral infections; Virus diseases; Viruses; United States > US; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0039757

The blocking of programmed death ligand-1 (PDL-1) has been shown to enhance virus-specific CD8 T cell function during chronic viral infections. Though, how PDL-1 blocking at the time of priming affects the quality of CD8 T cell response to acute infections is not well understood and remains controversial. This report demonstrates that the magnitude of the primary and secondary CD8 T cell responses to herpes simplex virus-1 (HSV-1) infection is subject to control by PDL-1. Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. Additionally, post-infection, the level of PDL-1 expression also increases on CD11c+ dendritic cells. Intraperitoneal administration of anti-PDL-1 monoclonal antibody given one day prior to and three days after cutaneous HSV-1 infection, resulted in a marked increase in effector and memory CD8 T cell response to SSIEFARL peptide. This was shown by measuring the quantity and quality of SSIEFARL-specific CD8 T cells by making use of ex-vivo assays that determine antigen specific CD8 T cell function, such as intracellular cytokine assay, degranulation assay to measure cytotoxicity and viral clearance. Our results are discussed in terms of the beneficial effects of blocking PDL-1 interactions, while giving prophylactic vaccines, to generate a more effective CD8 T cell response to viral infection.