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Pre-existing virus-specific CD8+ T-cells provide protection against pneumovirus-induced disease in mice

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van Helden, Mary J. G., Kooten, Peter J. S. van, Bekker, Cornelis P. J., Gröne, Andrea, Topham, David J., Easton, A. J. (Andrew J.), Boog, Claire J. P., Busch, Dirk H., Zaiss, Dietmar M. W. and Sijts, Alice J. A. M. (2012) Pre-existing virus-specific CD8+ T-cells provide protection against pneumovirus-induced disease in mice. Vaccine, Vol.30 (No.45). pp. 6382-6388. doi:10.1016/j.vaccine.2012.08.027

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Official URL: http://dx.doi.org/10.1016/j.vaccine.2012.08.027

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Abstract

Pneumoviruses such as pneumonia virus of mice (PVM), bovine respiratory syncytial virus (bRSV) or human (h)RSV are closely related pneumoviruses that cause severe respiratory disease in their respective hosts. It is well-known that T-cell responses are essential in pneumovirus clearance, but pneumovirus-specific T-cell responses also are important mediators of severe immunopathology. In this study we determined whether memory- or pre-existing, transferred virus-specific CD8 + T-cells provide protection against PVM-induced disease. We show that during infection with a sublethal dose of PVM, both natural killer (NK) cells and CD8 + T-cells expand relatively late. Induction of CD8 + T-cell memory against a single CD8 + T-cell epitope, by dendritic cell (DC)-peptide immunization, leads to partial protection against PVM challenge and prevents Th2 differentiation of PVM-induced CD4 T-cells. In addition, adoptively transferred PVM-specific CD8 + T-cells, covering the entire PVM-specific CD8 + T-cell repertoire, provide partial protection from PVM-induced disease. From these data we infer that antigen-specific memory CD8 + T-cells offer significant protection to PVM-induced disease. Thus, CD8 + T-cells, despite being a major cause of PVM-associated pathology during primary infection, may offer promising targets of a protective pneumovirus vaccine.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Pneumonia -- Prevention, T cells
Journal or Publication Title: Vaccine
Publisher: Elsevier Ltd.
ISSN: 0264-410X
Official Date: 2012
Dates:
DateEvent
2012Published
Volume: Vol.30
Number: No.45
Page Range: pp. 6382-6388
DOI: 10.1016/j.vaccine.2012.08.027
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: TI Pharma (Firm), Wellcome Trust (London, England)
Grant number: T4-214 (TIP), WT 085733MA (WT)

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