Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease

Thorburn, Alison N., O'Sullivan, Brendan J., Thomas, Ranjeny, Kumar, Rakesh K., Foster, Peter S., Gibson, Peter G. and Hansbro, Philip M. (2010) Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease. Thorax, 65 12: 1053-1060. doi:10.1136/thx.2009.131508


Author Thorburn, Alison N.
O'Sullivan, Brendan J.
Thomas, Ranjeny
Kumar, Rakesh K.
Foster, Peter S.
Gibson, Peter G.
Hansbro, Philip M.
Title Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease
Journal name Thorax   Check publisher's open access policy
ISSN 0040-6376
1468-3296
Publication date 2010-12
Sub-type Article (original research)
DOI 10.1136/thx.2009.131508
Volume 65
Issue 12
Start page 1053
End page 1060
Total pages 8
Place of publication London, United Kingdom
Publisher B M J Group
Collection year 2011
Language eng
Formatted abstract
Background Infections with some bacteria, including
Streptococcus pneumoniae, have been associated with
a reduced incidence of asthma. Components of S
pneumoniae
may have the potential to modulate allergic
inflammatory responses and suppress the development
of asthma.
Objectives To determine if human S pneumoniae
vaccines have the potential to suppress asthma by
elucidating their effect on allergic airways disease (AAD)
in mouse models.
Methods AAD was induced in BALB/c mice by
intraperitoneal sensitisation and intranasal challenge with
ovalbumin. Pneumococcal conjugate or polysaccharide
vaccines were administered at the time of sensitisation
or during established AAD. Hallmark features of AAD
were assessed. Levels of regulatory T cells (Tregs)
were quantified by fluorescence-activated cell
sorting, and their immunoregulatory capacity was
assessed using proliferation assays and anti-CD25
antibody treatment.
Results Intranasal administration of the conjugate
vaccine, but not the polysaccharide vaccine, suppressed
the hallmark features of AAD, including: eosinophilic and
T helper 2-mediated inflammation; airway hyperresponsiveness;
circulating immunoglobulin E (IgE) levels;
and mucus hypersecretion. Intramuscular administration
of the conjugate vaccine had limited protective effects.
The conjugate vaccine increased Tregs in the lungdraining
lymph nodes, lung and spleen. Furthermore,
conjugate vaccine-induced Tregs had an enhanced
capacity to suppress T effector responses. Anti-CD25
administration reversed the suppressive effects of the
conjugate vaccine.
Conclusions A currently available human conjugate
vaccine suppresses the hallmark features of AAD
through the induction of Tregs. Thus targeted
administration may provide a novel immunoregulatory
treatment for asthma.
Keyword Murine model
In-vivo
Asthma
Inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
 
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Created: Sun, 12 Dec 2010, 00:00:53 EST