Lung-resident memory CD8+ T cells prevent transmission of respiratory viruses

Abstract

Abstract Lung tissue-resident memory CD8+ T cells (TRM) reduce viral replication and limit pathology following respiratory virus infections. In particular, TRM are crucial for protection against infections with heterosubtypic influenza viruses, where pre-existing antibody does not provide sterilizing immunity. In addition to providing individual host immunity, vaccination programs are designed to limit pathogen spread at population level. Despite the interest in lung TRM for intra-host protective immunity, their effect on the transmission respiratory viruses has been understudied due to the lack of animal models where influenza infection can be tracked longitudinally, and where the immunological parameters are easily identified and manipulated. To circumvent these issues, we used a luciferase-expressing Sendai virus, a natural mouse parainfluenza virus that readily transmits via the aerosol and contact routes, to evaluate the efficacy of lung TRM against transmission of respiratory viruses. Using a recombinant influenza virus expressing the immunodominant SenNP324–332Kb epitope to generate SenNP+ memory CD8+ T cells and IVIS imaging to non-invasively measure Sendai virus infection over time, we found that mice with pre-existing SenNP+ lung TRM don’t transmit Sendai virus to naïve mice when co-housed. In contrast, immunized mice that had pre-existing circulating effector memory CD8+ T cells (TEM), but no lung TRM, failed to prevent transmission of Sendai virus to naïve mice when co-housed. These results show the ability of lung TRM to contribute to herd immunity by preventing respiratory virus transmission and underscore the potential of a TRM-inducing vaccine for protection against respiratory viruses.