Cytotoxic T cells are the predominant players providing cross-protective immunity induced by {gamma}-irradiated influenza A viruses.
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.
Furuya
Yoichi
Y
Viral Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
Chan
Jennifer
J
Regner
Matthias
M
Lobigs
Mario
M
Koskinen
Aulikki
A
Kok
Tuckweng
T
Manavis
Jim
J
Li
Peng
P
Müllbacher
Arno
A
Alsharifi
Mohammed
M
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D056738:Cross Protection; D005720:Gamma Rays; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000528:radiation effects; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000528:radiation effects; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated