Induction of homotypic and heterotypic T- and B-cell immunity with influenza A virus in mice

Infection of mice with live influenza A virus induces cytolytic T lymphocytes (CTL) as well as B cells capable of reacting with target cells infected with the appropriate virus subtypes. In Balb/c mice CTL reveal a broad cross-reactivity against all influenza A substrains known. In contrast B-cell responses are restricted to virus subtypes which are identical in regard to the hemagglutinin (HA) of the sensitizing virus. Reinfection with homologous live influenza virus within 6–7 months results in no or in a drastically diminished B-cell response as compared to a priming situation and fails to induce CTL. Inability to induce secondary immunity to homologous influenza virus was correlated with the presence of circulating antibodies specific for the sensitizing virus subtype. Cross-boosting with heterologous live influenza A virus induces homotypic and heterotypic CTL and B-cell immunity with characteristics of secondary responses. Preparations of inactivated intact influenza virus are unable to reactivate CTL memory in vivo but induce B-cell activity. B-cell responses stimulated by this procedure are restricted to the boosting virus. Attenuated viruses, which are produced by recombination of wild strains with cold-adapted strains, are also efficient in stimulating in vivo CTL memory if used for cross-boosting.