Blocking of PDL-1 interaction enhances primary and secondary CD8 t cell response to herpes simplex virus-1 infection

Rudragouda Channappanavar, Brandon S. Twardy, Susmit Suvas

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere39757
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 12 2012

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Human herpesvirus 1
T-cells
Human Herpesvirus 1
Virus Diseases
Viruses
T-lymphocytes
death
Ligands
T-Lymphocytes
infection
cells
Assays
assays
peptides
CD8 Antigens
Peptides
ligands
dendritic cells
Cytotoxicity
intraperitoneal injection

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Blocking of PDL-1 interaction enhances primary and secondary CD8 t cell response to herpes simplex virus-1 infection. / Channappanavar, Rudragouda; Twardy, Brandon S.; Suvas, Susmit.

In: PloS one, Vol. 7, No. 7, e39757, 12.07.2012.

Research output: Contribution to journalArticle

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