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|Title:||Cytoxic T cells are the predominant players providing cross-protective immunity induced by y-irradiated influenza A viruses|
|Citation:||Journal of Virology, 2010; 84(9):4212-4221|
|Publisher:||Amer Soc Microbiology|
|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; Animals; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice; 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.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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