How does the immune system respond to a viral infection?

This week CBR member Susmit Suvas, of the Department of Biological Sciences, published a paper in PLoS ONE, the flagship journal of the Public Library of Science that features articles from all fields of science. Suvas’s coauthors are his two stellar graduate students, Brandon Twardy and lead author Rudragouda Channappanavar, who both recently competed the Biomedical Sciences: Biological Communication PhD program. The paper is titled Blocking of PDL-1 Interaction Enhances Primary and Secondary CD8 T Cell Response to Herpes Simplex Virus-1 Infection (7:e39757, 2012). The article explores the response of the immune system to viral infection, and may have implications for improving the effectiveness of vaccines. The abstract is given below.

“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.”

Rudragouda Channappanavar recently began a post doc at the University of Iowa with Dr. Stanley Perlman, a leader in the field of immunology. Brandon Twardy has enrolled at Wayne State Medical School this fall, with the goal of obtaining a WSU MD to go with his OU PhD.

Suvas’s research was supported by an American Federation for Aging Research Grant, the grant R21EY020625 from the National Eye Institute (one of the National Institutes of Health), and the Oakland University Research Excellence Fund administered by the CBR.