Upper respiratory tract CD8+ tissue-resident memory T cells protect against viral transmission

Intranasal vaccination elicits CD8 tissue-resident memory T cells (TRM) throughout the respiratory tract that provide cross-protection against heterosubtypic viral strains and reduce immunopathology. We previously demonstrated that CD8 TRM can reduce the probability of respiratory virus transmission and the magnitude of infection, using a murine model of parainfluenza virus transmission. Here, we show that CD8 TRM-mediated protection occurs independently of circulating leukocytes, B cells, or CD4 T cells. Additionally, we investigate the contributions of CD8 TRM in different respiratory tract compartments and illustrate that CD8 TRM in the upper respiratory tract (URT), but not the lower respiratory tract (LRT), become activated and proliferate in response to transmitted virus. Furthermore, we demonstrate that CD8 TRM in the URT alone provide sufficient immune surveillance to prevent propagation of infection after viral transmission. These findings offer insights into the development of T cell-based respiratory virus vaccines and shed light on the critical role of URT CD8 TRM in the prevention of viral transmission.