The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia

Matthew R Olson; Stacey M Hartwig; Steven M Varga

doi:10.4049/jimmunol.181.11.7958

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The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia

Journal article

Peer reviewed

The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia

Matthew R Olson, Stacey M Hartwig and Steven M Varga

The Journal of immunology (1950), Vol.181(11), pp.7958-7968

12/01/2008

DOI: 10.4049/jimmunol.181.11.7958

PMCID: PMC2587004

PMID: 19017987

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Abstract

Children that were administered a formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine experienced enhanced respiratory disease, including pulmonary eosinophilia, after contracting a natural RSV infection. RSV vaccine-enhanced disease can be mimicked in BALB/c mice immunized with either FI-RSV or with a recombinant vaccinia virus (vacv) expressing the RSV attachment (G) protein. We have recently demonstrated that memory CD8 T cells directed against the RSV immunodominant M2(82-90) epitope inhibit the development of pulmonary eosinophilia in either vacvG- or FI-RSV-immunized mice by reducing the total number of Th2 cells in the lung after RSV challenge. In this study, we show that memory CD8 T cells specific to a subdominant epitope within the RSV fusion (F) protein fail to inhibit the development of pulmonary eosinophilia after RSV challenge of mice previously co-immunized with vacvF and with either vacvG or FI-RSV. We observed that the inability of RSV F(85)-specific memory CD8 T cells to inhibit the development of pulmonary eosinophilia was largely due to an inadequate total number of F(85)-specific memory CD8 T cells in the lung at early times after RSV challenge. Increasing the number of F(85)-specific memory CD8 T cells after immunization grants these cells the ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia. Moreover, we demonstrate that RSV-specific memory CD8 T cells, when present in sufficient numbers, inhibit the production of the Th2-associated chemokines CCL17 and CCL22. Taken together, these results indicate that RSV-specific memory CD8 T cells may alter the trafficking of Th2 cells and eosinophils into the lung.

Respiratory Syncytial Virus Vaccines - immunology

Humans

Respiratory Syncytial Viruses - immunology

Child, Preschool

Epitopes, T-Lymphocyte - genetics

Male

Th2 Cells - immunology

Immunologic Memory - drug effects

Eosinophils - immunology

Respiratory Syncytial Virus Infections - immunology

Vaccinia virus - genetics

Vaccinia virus - immunology

Cell Movement - immunology

Respiratory Syncytial Virus Vaccines - adverse effects

Chemokine CCL22 - immunology

Chemokine CCL17 - immunology

Respiratory Syncytial Virus Infections - prevention & control

Female

Epitopes, T-Lymphocyte - immunology

Child

Immunologic Memory - immunology

Disease Models, Animal

Viral Envelope Proteins - genetics

Mice, Knockout

Vaccines, Inactivated - adverse effects

Vaccines, Inactivated - immunology

Animals

Eosinophilia - immunology

Respiratory Syncytial Viruses - genetics

Eosinophilia - prevention & control

Viral Envelope Proteins - immunology

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

Respiratory Syncytial Virus Vaccines - genetics

Lung - immunology

Details

Title: Subtitle: The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia
Creators: Matthew R Olson - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Stacey M Hartwig
Steven M Varga
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.181(11), pp.7958-7968
DOI: 10.4049/jimmunol.181.11.7958
PMID: 19017987
PMCID: PMC2587004
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI-063520 / NIAID NIH HHS R01 AI063520-02 / NIAID NIH HHS R01 AI063520 / NIAID NIH HHS
Language: English
Date published: 12/01/2008
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984083208702771

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