Type 1 interferon licenses naïve CD8 T cells to mediate anti-viral cytotoxicity

Naïve T cells, unlike memory T cells, exhibit very limited effector function in response to cognate antigen, but exposure to type 1 interferon (IFN) prior to cognate antigen allows for rapid manifestation of effector functions. A full assessment of the functions of these IFN-sensitized otherwise naïve T cells has not been made, nor has their capacity to be effector cells in vivo. We describe here that IFN-sensitized naïve T cells in the absence of cognate antigen adopt a partial activated phenotype distinguished by the upregulation of the surface activation marker CD69, effector-associated transcription factors Eomes and IRF4, and cytotoxicity effector molecule granzyme B. IFN-sensitized naive T cells lysed target cells in vivo and responded to low concentrations and affinities of cognate ligands. We suggest that this rapid and sensitive effector function of IFN-conditioned naïve CD8 T cells may play a role in pathogen control and help ward off superinfections.