Persistence of influenza as an immunogen in pulmonary antigen-presenting cells

Influenza antigens inoculated into the lung induce local immune responses. It has been proposed that this induction might be partly regulated by local antigen-presenting cells. The purpose of the current study was to inoculate heat-inactivated influenza virus into the tracheae of guinea pigs and determine the quantity of antigens that became cell-associated. Second, we determined how long antigen-presenting bronchoalveolar cells that had taken up virus in vivo retained their ability to specifically stimulate virus-immune T lymphocytes. Radioiodinated heat-inactivated influenza virus was inoculated into the tracheae of guinea pigs. The animals were killed from 30 min to 14 days after intratracheal inoculation, and radioactivity was determined in cells isolated from lung tissue. At least one-third of the radioactivity in the lungs was cell-associated from 1 to 14 days post-inoculation. In separate studies, heat-inactivated virus was inoculated into the airways of guinea pigs, and animals were killed at various times thereafter. Bronchoalveolar cells from these animals were compared with those from uninoculated controls in their ability to specifically stimulate virus-immune T cells to proliferate in vitro. Bronchoalveolar cells from virus-inoculated animals specifically stimulated T lymphocytes for up to 7 days after virus inoculation. These studies suggest that immunogenic virus persists in the lung within antigen-presenting cells for at least 1 week and possibly for up to 2 weeks. The persisting immunogenic stimulus after the termination of viral infections might be critical in ensuring the development of a local protective immune response.