Type 1 interferon primes naïve CD8 T cells to respond to lower concentrations and affinities of cognate ligands (VIR6P.1178)

Abstract During an acute virus infection, antigen-specific CD8 T cells undergo clonal expansion and differentiation into effector cells in order to control the infection. Studies have shown that CD8 T cells need to divide at least once before they acquire specific effector functions, including the ability to directly lyse target cells and produce certain cytokines. However, recently we have shown that pre-exposure of the host to type I interferon (IFN) sensitizes CD8 T cells to rapidly acquire effector function without the need to divide. The IFN-primed naïve CD8 T cells produced IFNγ, enhanced TNF and degranulated upon stimulation with high affinity cognate antigen. The threshold required for IFN-induced sensitized CD8 T cells to become activated and produce effector functions was reduced, as primed CD8 T cells produced cytokines in response to lower affinity ligands and lower concentrations of cognate ligands. In addition, an in vivo cytotoxicity assay showed that primed naïve CD8 T cells specifically lysed target cells. The reduced requirement of naïve CD8 T cells to produce effector functions if pre-exposed to IFN-induced environments may increase the overall number of naïve T cells able to respond to any given antigen. IFN-primed increased numbers and response of naïve T cells may help to control antigen load during an acute infection.