CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2

Tissue-resident memory CD8+ T (CD8 T RM ) cells are an essential component of protective immune responses at barrier tissues, including the female genital tract. However, the mechanisms that lead to the initiation of CD8 T RM -mediated protective immunity after viral infection are unclear. Here we report that CD8 T RM cells established by ‘prime and pull’ method confer protection against genital HSV-2 infection, and that IFN-γ produced by CD8 T RM cells is required for this protection. Furthermore, we find that CD8 T RM -cell restimulation depends on a population of CD301b + antigen-presenting cells (APC) in the lamina propria. Elimination of MHC class I on CD301b + dendritic cells abrogates protective immunity, suggesting the requirement for cognate antigen presentation to CD8 T RM cells by CD301b + dendritic cells. These results define the requirements for CD8 T RM cells in protection against genital HSV-2 infection and identify the population of APC that are responsible for activating these cells.