Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection

Megan E Schmidt; Cory J Knudson; Stacey M Hartwig; Lecia L Pewe; David K Meyerholz; Ryan A Langlois; John T Harty; Steven M Varga

doi:10.1371/journal.ppat.1006810

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Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection

Journal article

Open access

Peer reviewed

Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection

Megan E Schmidt, Cory J Knudson, Stacey M Hartwig, Lecia L Pewe, David K Meyerholz, Ryan A Langlois, John T Harty and Steven M Varga

PLoS pathogens, Vol.14(1), pp.e1006810-e1006810

01/02/2018

DOI: 10.1371/journal.ppat.1006810

PMCID: PMC5766251

PMID: 29293660

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Abstract

Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.

Severity of Illness Index

Immune System Diseases - virology

Humans

Respiratory Syncytial Viruses - immunology

Cells, Cultured

Immune System Diseases - immunology

Respiratory Syncytial Virus Infections - immunology

CD8-Positive T-Lymphocytes - physiology

Animals

Female

Immunologic Memory

Mice

Mice, Inbred BALB C

Respiratory Syncytial Virus Infections - pathology

Immune System Diseases - pathology

Respiratory Syncytial Virus Infections - complications

Details

Title: Subtitle: Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection
Creators: Megan E Schmidt - University of Iowa, Microbiology and Immunology
Cory J Knudson - University of Iowa
Stacey M Hartwig - University of Iowa, Microbiology and Immunology
Lecia L Pewe - University of Iowa
David K Meyerholz - University of Iowa, Pathology
Ryan A Langlois - University of Minnesota
John T Harty - University of Iowa, Microbiology and Immunology
Steven M Varga - University of Iowa, Microbiology and Immunology
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.14(1), pp.e1006810-e1006810
DOI: 10.1371/journal.ppat.1006810
PMID: 29293660
PMCID: PMC5766251
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: United States
Grant note: P30 DK054759 / NIDDK NIH HHS\r\nR01 AI124093 / NIAID NIH HHS
Language: English
Date published: 01/02/2018
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Community and Behavioral Health
Record Identifier: 9983769581002771

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