CD8 T cells utilize TRAIL to control influenza virus infection

Erik L Brincks; Arna Katewa; Tamara A Kucaba; Thomas S Griffith; Kevin L Legge

doi:10.4049/jimmunol.181.7.4918

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CD8 T cells utilize TRAIL to control influenza virus infection

Journal article

Peer reviewed

CD8 T cells utilize TRAIL to control influenza virus infection

Erik L Brincks, Arna Katewa, Tamara A Kucaba, Thomas S Griffith and Kevin L Legge

The Journal of immunology (1950), Vol.181(7), pp.4918-4925

10/01/2008

DOI: 10.4049/jimmunol.181.7.4918

PMCID: PMC2610351

PMID: 18802095

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Abstract

Elimination of influenza virus-infected cells during primary influenza virus infections is thought to be mediated by CD8(+) T cells though perforin- and FasL-mediated mechanisms. However, recent studies suggest that CD8(+) T cells can also utilize TRAIL to kill virally infected cells. Therefore, we herein examined the importance of TRAIL to influenza-specific CD8(+) T cell immunity and to the control of influenza virus infections. Our results show that TRAIL deficiency increases influenza-associated morbidity and influenza virus titers, and that these changes in disease severity are coupled to decreased influenza-specific CD8(+) T cell cytotoxicity in TRAIL(-/-) mice, a decrease that occurs despite equivalent numbers of pulmonary influenza-specific CD8(+) T cells. Furthermore, TRAIL expression occurs selectively on influenza-specific CD8(+) T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells. Finally, we show that adoptive transfer of TRAIL(+/+) but not TRAIL(-/-) CD8(+) effector T cells alters the mortality associated with lethal dose influenza virus infections. Collectively, our results suggest that TRAIL is an important component of immunity to influenza infections and that TRAIL deficiency decreases CD8(+) T cell-mediated cytotoxicity, leading to more severe influenza infections.

Influenza A Virus, H1N1 Subtype - immunology

Orthomyxoviridae Infections - prevention & control

CD8-Positive T-Lymphocytes - cytology

Apoptosis - genetics

Influenza A Virus, H1N1 Subtype - growth & development

Viral Load

Lung - virology

TNF-Related Apoptosis-Inducing Ligand - biosynthesis

TNF-Related Apoptosis-Inducing Ligand - deficiency

Weight Loss - immunology

Weight Loss - genetics

Cell Line

Lung - pathology

Mice, Inbred C57BL

Orthomyxoviridae Infections - pathology

Mice, Knockout

Animals

Apoptosis - immunology

Orthomyxoviridae Infections - mortality

TNF-Related Apoptosis-Inducing Ligand - physiology

CD8-Positive T-Lymphocytes - virology

Mice

CD8-Positive T-Lymphocytes - immunology

Orthomyxoviridae Infections - virology

TNF-Related Apoptosis-Inducing Ligand - genetics

Lung - immunology

Details

Title: Subtitle: CD8 T cells utilize TRAIL to control influenza virus infection
Creators: Erik L Brincks - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Arna Katewa
Tamara A Kucaba
Thomas S Griffith
Kevin L Legge
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.181(7), pp.4918-4925
DOI: 10.4049/jimmunol.181.7.4918
PMID: 18802095
PMCID: PMC2610351
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 R21 AI072032-01A1 / NIAID NIH HHS
Language: English
Date published: 10/01/2008
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047718802771

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