RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets

Cory J Knudson; Stacey M Hartwig; David K Meyerholz; Steven M Varga

doi:10.1371/journal.ppat.1004757

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RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets

Journal article

Open access

Peer reviewed

RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets

Cory J Knudson, Stacey M Hartwig, David K Meyerholz and Steven M Varga

PLoS pathogens, Vol.11(3), pp.e1004757-23

03/2015

DOI: 10.1371/journal.ppat.1004757

PMCID: PMC4358888

PMID: 25769044

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Abstract

There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. Children previously immunized with a formalin-inactivated RSV (FI-RSV) vaccine exhibited enhanced respiratory disease following natural RSV infection. Subsequent studies in animal models have implicated roles for CD4 T cells, eosinophils and non-neutralizing antibodies in mediating enhanced respiratory disease. However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. We demonstrate for the first time that while CD4 T cells mediate all aspects of vaccine-enhanced disease, distinct CD4 T cell subsets orchestrate discrete and specific disease parameters. A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF-α was necessary to mediate airway obstruction and weight loss. Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells.

Respiratory Syncytial Virus Vaccines - immunology

Animals

Humans

Respiratory Syncytial Viruses - immunology

Tumor Necrosis Factor-alpha - genetics

Tumor Necrosis Factor-alpha - immunology

Mice

Mice, Inbred BALB C

Th2 Cells - immunology

Th1 Cells - immunology

Mice, Knockout

Details

Title: Subtitle: RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets
Creators: Cory J Knudson - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America
Stacey M Hartwig - Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America
Steven M Varga - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America; Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.11(3), pp.e1004757-23
DOI: 10.1371/journal.ppat.1004757
PMID: 25769044
PMCID: PMC4358888
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: Public Library of Science
Grant note: R01 AI063520 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS R56 AI106776 / NIAID NIH HHS R56AI106776 / NIAID NIH HHS R01AI063520 / NIAID NIH HHS T32AI007485 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 03/2015
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984083270402771

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