Resident Memory CD8+ T cells in the respiratory tract prevent transmission of respiratory viruses

Abstract

Abstract Tissue-resident memory CD8+ T cells (TRM) in the respiratory tract reduce viral replication and limit pathology following respiratory virus infections. In infection with heterosubtypic influenza viruses, where pre-existing antibodies does not proved sterilizing immunity, TRM are critical for protection. However, in addition to protecting the host against disease vaccine programs are also designed to limit viral spread in a population. Due to the lack of an animal model to study the effect of TRM on transmission through longitudinal tracking, and with immunological parameters easily identified and manipulated available, this hasn’t been studied before. To solve these issues, we used a luciferase expressing Sendai virus, a natural mouse parainfluenza virus that readily transmits via the aerosol and contact routes, as well as a recombinant influenza virus expressing the immunodominant Sendai NP324-332/Kb epitope to generate SenNP+ memory CD8+ T cells. By utilizing IVIS imaging to non-invasively measure Sendai virus infection over time, we found that mice with pre-existing SenNP+ TRM in the respiratory system don’t transmit Sendai virus to naïve mice when co-housed. In contrast, mice with pre-existing circulating SenNP+ effector memory CD8+ T cells, but no TRM, failed to prevent transmission of Sendai virus to naïve mice when co-housed. In addition, we found that the prevention of transmission was dependent on the production of IFNγ. These findings demonstrates notably that antigen specific lung TRM contributes to herd immunity by preventing respiratory virus transmission. This underscores the importance, and potential, of TRMs generated by vaccines for protection against respiratory viruses.