Document Detail


Cytotoxic T cells are the predominant players providing cross-protective immunity induced by {gamma}-irradiated influenza A viruses.
MedLine Citation:
PMID:  20164231     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously demonstrated that a single dose of nonadjuvanted intranasal gamma-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. Furthermore, gamma-irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4(+) and CD8(+), and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with gamma-irradiated influenza A virus is mediated mainly by Tc-cell responses.
Authors:
Yoichi Furuya; Jennifer Chan; Matthias Regner; Mario Lobigs; Aulikki Koskinen; Tuckweng Kok; Jim Manavis; Peng Li; Arno Müllbacher; Mohammed Alsharifi
Publication Detail:
Type:  Journal Article     Date:  2010-02-17
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-07     Completed Date:  2010-04-21     Revised Date:  2010-11-02    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4212-21     Citation Subset:  IM    
Affiliation:
Viral Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
Antibodies, Viral / blood
Body Weight
Cross Protection*
Gamma Rays*
Influenza A Virus, H1N1 Subtype / immunology*,  radiation effects
Influenza A Virus, H3N2 Subtype / immunology*,  radiation effects
Influenza Vaccines / immunology*
Lung / pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections / immunology,  prevention & control
Survival Analysis
T-Lymphocytes, Cytotoxic / immunology*
Vaccines, Inactivated / immunology
Chemical
Reg. No./Substance:
0/Antibodies, Viral; 0/Influenza Vaccines; 0/Vaccines, Inactivated

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