Figure 9. Model of the mechanisms that sensitize bystander CD8 T cells during acute viral infections.
IFN-αβ induced by viral infection or TLR agonist poly(I:C) induces expression of IL-15 and up-regulation of MHC I. Up-regulation of MHC I enhances presentation of self and virus-encoded peptides, which signal through the TCR of bystander CD8 T cells, inducing Eomes expression. Eomes induces expression of CD122, which confers IL-15 responsiveness and induces GrzB expression. In response to cognate antigen, the expression of Eomes allows for the rapid synthesis of IFN-γ. IL-15 expression is also required for the enhanced cognate antigen-driven degranulation.