The magnitude of the T cell response to a clinically significant dose of influenza virus is regulated by TRAIL

Erik L Brincks; Prajwal Gurung; Ryan A Langlois; Emily A Hemann; Kevin L Legge; Thomas S Griffith

doi:10.4049/jimmunol.1002241

Back

The magnitude of the T cell response to a clinically significant dose of influenza virus is regulated by TRAIL

Journal article

Peer reviewed

The magnitude of the T cell response to a clinically significant dose of influenza virus is regulated by TRAIL

Erik L Brincks, Prajwal Gurung, Ryan A Langlois, Emily A Hemann, Kevin L Legge and Thomas S Griffith

The Journal of immunology (1950), Vol.187(9), pp.4581-4588

11/01/2011

DOI: 10.4049/jimmunol.1002241

PMCID: PMC3197947

PMID: 21940678

View Online

Abstract

An immune response of appropriate magnitude should be robust enough to control pathogen spread but not simultaneously lead to immunopathology. Primary infection with influenza A virus (IAV) results in a localized pulmonary infection and inflammation and elicits an IAV-specific CD8 T cell immune response necessary for viral clearance. Clearance of IAV-infected cells, and recovery from infection, is mediated by perforin/granzyme B- and Fas/FasL-mediated mechanisms. We recently reported that TRAIL is another means by which IAV-specific CD8 T cells can kill IAV-infected cells. The current study examined the role of TRAIL in the pulmonary CD8 T cell response to a clinically significant IAV [A/PR/8/34 (PR8; H1N1)] infection (i.e., leads to observable, but limited, morbidity and mortality in wild-type [WT] mice). Compared with WT mice, IAV-infected Trail(-/-) mice experienced increased morbidity and mortality despite similar rates of viral clearance from the lungs. The increased morbidity and mortality in Trail(-/-) mice correlated with increased pulmonary pathology and inflammatory chemokine production. Analysis of lung-infiltrating lymphocytes revealed increased numbers of IAV-specific CD8 T cells in infected Trail(-/-) mice, which correlated with increased pulmonary cytotoxic activity and increased pulmonary expression of MIG and MIP-1α. In addition, there was decreased apoptosis and increased proliferation of IAV-specific CD8 T cells in the lungs of Trail(-/-) mice compared with WT mice. Together, these data suggest that TRAIL regulates the magnitude of the IAV-specific CD8 T cell response during a clinically significant IAV infection to decrease the chance for infection-induced immunopathology.

Influenza A Virus, H1N1 Subtype - immunology

Lung - pathology

CD8-Positive T-Lymphocytes - pathology

Dose-Response Relationship, Immunologic

Mice, Inbred C57BL

Influenza A Virus, H3N2 Subtype - immunology

Mice, Knockout

Lung - virology

Animals

Orthomyxoviridae Infections - mortality

TNF-Related Apoptosis-Inducing Ligand - physiology

CD8-Positive T-Lymphocytes - virology

Survival Analysis

TNF-Related Apoptosis-Inducing Ligand - deficiency

Mice

Mice, Inbred BALB C

Epitopes, T-Lymphocyte - immunology

CD8-Positive T-Lymphocytes - immunology

Orthomyxoviridae Infections - virology

TNF-Related Apoptosis-Inducing Ligand - genetics

Lung - immunology

Orthomyxoviridae Infections - immunology

Details

Title: Subtitle: The magnitude of the T cell response to a clinically significant dose of influenza virus is regulated by TRAIL
Creators: Erik L Brincks - Department of Urology, University of Iowa, Iowa City, IA 52242, USA
Prajwal Gurung
Ryan A Langlois
Emily A Hemann
Kevin L Legge
Thomas S Griffith
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.187(9), pp.4581-4588
DOI: 10.4049/jimmunol.1002241
PMID: 21940678
PMCID: PMC3197947
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R21 AI072032 / NIAID NIH HHS R21 AI072032-02 / NIAID NIH HHS R56 AI077565-01A1 / NIAID NIH HHS AI 072032 / NIAID NIH HHS R56 AI077565 / NIAID NIH HHS AI 077565 / NIAID NIH HHS R01 CA109446 / NCI NIH HHS
Language: English
Date published: 11/01/2011
Academic Unit: Microbiology and Immunology; Infectious Diseases; Pathology; Internal Medicine
Record Identifier: 9984047975802771

Metrics

28 Record Views

33 Times Cited - Web of Science