Blocking of PDL-1 interaction enhances primary and secondary CD8 T cell response to herpes simplex virus-1 infection.
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.
Department of Biological Sciences, Oakland University, Rochester, Michigan, United States of America.
Rudragouda
R
Channappanavar
Brandon S
BS
Twardy
Susmit
S
Suvas
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007118:Immunoassay; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D039521:CD11c Antigen; C498919:Cd274 protein, mouse; D016056:Immunodominant Epitopes; D009842:Oligopeptides