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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Article numbere1006810
JournalPLoS pathogens
Volume14
Issue number1
DOIs
StatePublished - Jan 2018

Bibliographical note

Funding Information:
Research reported in this publication was supported by funds from the Department of Microbiology at the University of Iowa (to SMV) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers R01AI124093 (to SMV) T32AI007485 (to CJK and MES). Research reported in this publication was also supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA086862. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Some of the data presented herein were obtained at the Flow Cytometry Facility, which is a Carver College of Medicine / Holden Comprehensive Cancer Center core research facility at the University of Iowa.

Publisher Copyright:
© 2018 Schmidt et al.

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