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Type: Journal article
Title: Cytoxic T cells are the predominant players providing cross-protective immunity induced by y-irradiated influenza A viruses
Author: Furuya, Y.
Chan, J.
Regner, M.
Lobigs, M.
Koskinen, A.
Kok, T.
Manavis, J.
Li, P.
Mullbacher, A.
Alsharifi, M.
Citation: Journal of Virology, 2010; 84(9):4212-4221
Publisher: Amer Soc Microbiology
Issue Date: 2010
ISSN: 0022-538X
Statement of
Yoichi Furuya, Jennifer Chan, Matthias Regner, Mario Lobigs, Aulikki Koskinen, Tuckweng Kok, Jim Manavis, Peng Li, Arno Müllbacher, and Mohammed Alsharifi
Abstract: We previously demonstrated that a single dose of nonadjuvanted intranasal -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, -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 -irradiated influenza A virus is mediated mainly by Tc-cell responses.
Keywords: Lung
T-Lymphocytes, Cytotoxic
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections
Body Weight
Vaccines, Inactivated
Influenza Vaccines
Antibodies, Viral
Adoptive Transfer
Survival Analysis
Gamma Rays
Influenza A Virus, H3N2 Subtype
Influenza A Virus, H1N1 Subtype
Cross Protection
Rights: Copyright © 2010, American Society for Microbiology. All Rights Reserved.
DOI: 10.1128/JVI.02508-09
Published version:
Appears in Collections:Aurora harvest 5
IPAS publications
Molecular and Biomedical Science publications

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