We characterized the in vivo primary and secondary murine CD8+ T cell responses induced by immunization with influenza and vaccinia viruses, which were engineered to express the same H-2K(k)- and H-2K(d)-restricted epitopes. Our results show that the induction and magnitude of the primary CD8+ T cell response closely depends on the viral dose used for immunization, while it is not affected by the route of immunization. The induction of secondary CD8+ T cell responses appears to be highly restricted, as suggested by the lack of in vivo expansion of antigen-specific CD8+ T cells after repeated immunization with the same virus. In contrast, a 20- to 30-fold increase in the frequency of antigen-specific CD8+ T cells could be induced after combined immunization with recombinant influenza and vaccinia viruses. These findings may provide the basis for the development of new prophylactic and therapeutic strategies to prevent or control intracellular infections and certain malignancies.
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