Elsevier

Vaccine

Volume 30, Issue 45, 5 October 2012, Pages 6382-6388
Vaccine

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

https://doi.org/10.1016/j.vaccine.2012.08.027Get rights and content
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open access

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.

Highlights

► NK cells and CD8+ T-cells expand relatively late following pneumovirus infection. ► Memory CD8+ T-cells support type 1 skewing of pneumovirus-specific responses. ► Memory CD8+ T-cells prevent pneumovirus-induced immunopathology. ► CD8+ T-cell targeted immunization protects against pneumovirus-induced disease.

Abbreviations

BAL
bronchoalveolar lavage
BALF
BAL fluid
DC
dendritic cell
BM-DC
bone marrow derived DC
DCp
peptide-loaded DC
FI
formalin inactivated
hRSV
human respiratory syncytial virus
ID
infectious dose
EID
egg ID
i.n.
intranasal
i.p.
intraperitoneal
i.v.
intravenous
MLN
mediastinal lymph node
NK
natural killer
NS
nonstructural
p.i.
post infection
pfu
plaque forming units
PVM
pneunomia virus of mice
SEM
standard error of mean

Keywords

Pneumoviruses
Pneunomia virus of mice
NK cell
CD8+ T-cell
Vaccine

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