Microbial exposure remodels and increases combat readiness of the naïve CD8 T cell compartment via type I interferons

Studies in specific pathogen-free mice revealed that naïve T (Tn) cells require two homeostatic signals for long-term survival–the sub-threshold T cell receptor:self-peptide–MHC contact, and IL-7 stimulation. It is not known how microbial exposure impacts Tn homeostasis. We report that the presence of infections led to expansion of a novel subpopulation of long-lived, Ly6C+ Tn cells with rapid effector function. Monoinfection with West Nile virus transiently, and polymicrobial exposure persistently, enhanced Ly6C expression on CD5hi cells, the latter yielding a numerical Tn cell increase in the lymph nodes. Conversion and expansion of Ly6C+ Tn cells depended on IFN-I, that upregulated MHC class I expression and enhanced trophic TCR signaling in Tn cells. IFN-I-mediated signals extended lifespan, optimized homing to secondary and tertiary sites, and drove Ly6C+ Tn cells to higher “combat readiness” as judged by increased effector differentiation. Thereby, infection-driven IFN-I powerfully modulates Tn homeostasis and function. 2x10e5 CD8+CD62L+CD44loLy6C+ and Ly6C- naïve T cells were isolated from 4 SPF and 4 cohoused mice using a CD8a+ T cell isolation kit (Miltenyi Biotec) followed by FACS Aria III sorting (BD Biosciences).