Vβ14+ T Cells Mediate the Vaccine-Enhanced Disease Induced by Immunization with Respiratory Syncytial Virus (RSV) G Glycoprotein but Not with Formalin-Inactivated RSV

Teresa R Johnson; Steven M Varga; Thomas J Braciale; Barney S Graham

doi:10.1128/JVI.78.16.8753-8760.2004

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Vβ14+ T Cells Mediate the Vaccine-Enhanced Disease Induced by Immunization with Respiratory Syncytial Virus (RSV) G Glycoprotein but Not with Formalin-Inactivated RSV

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Vβ14+ T Cells Mediate the Vaccine-Enhanced Disease Induced by Immunization with Respiratory Syncytial Virus (RSV) G Glycoprotein but Not with Formalin-Inactivated RSV

Teresa R Johnson, Steven M Varga, Thomas J Braciale and Barney S Graham

Journal of virology, Vol.78(16), pp.8753-8760

08/2004

DOI: 10.1128/JVI.78.16.8753-8760.2004

PMCID: PMC479099

PMID: 15280483

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Abstract

Mice immunized with respiratory syncytial virus (RSV) G glycoprotein or with formalin-inactivated RSV (FI-RSV) exhibit severe disease following RSV challenge. This results in type 2 cytokine production and pulmonary eosinophilia, both hallmarks of vaccine-enhanced disease. RSV G-induced T-cell responses were shown to be restricted to CD4 + T cells expressing Vβ14 in the T-cell receptor (TCR), and the deletion of these T cells resulted in less severe disease. We therefore examined the role of Vβ14 + T cells in FI-RSV-induced disease. BALB/c mice were immunized with vaccinia virus expressing secreted RSV G (vvGs) or with FI-RSV. At the time of challenge with live RSV, mice were injected with antibody to the Vβ14 component of the TCR. vvGs-immunized mice treated with anti-Vβ14 had reduced cytokine levels in the lung. Eosinophil recruitment to the lung was also significantly reduced. In contrast, depletion of Vβ14 + T cells in FI-RSV-immunized mice had little impact on cytokine production or pulmonary eosinophilia. An analysis of TCR Vβ chain usage confirmed a bias toward Vβ14 expression on CD4 + T cells from vvGs-immunized mice, whereas the CD4 + T cells in FI-RSV-immunized mice expressed a diverse array of Vβ chains. These data show that although FI-RSV and vvGs induce responses resulting in similar immunopathology, the T-cell repertoire mediating the response is different for each immunogen and suggest that the immune responses elicited by RSV G are not the basis for FI-RSV vaccine-enhanced disease.

Pathogenesis and Immunity

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Title: Subtitle: Vβ14+ T Cells Mediate the Vaccine-Enhanced Disease Induced by Immunization with Respiratory Syncytial Virus (RSV) G Glycoprotein but Not with Formalin-Inactivated RSV
Creators: Teresa R Johnson - Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Steven M Varga - Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Thomas J Braciale - Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Barney S Graham - Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Resource Type: Journal article
Publication Details: Journal of virology, Vol.78(16), pp.8753-8760
DOI: 10.1128/JVI.78.16.8753-8760.2004
PMID: 15280483
PMCID: PMC479099
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 08/2004
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984083880702771

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