Early microbial exposure shapes adult immunity by altering CD8+ T cell development [RNA-seq]

Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the setpoint for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a new conceptual framework for understanding how microbial colonization in early life leads to lifelong, and potentially irreversible, changes in the immune system. Overall design: Gene profile analysis was performed on FACS purified naive fetal- and adult-derived CD8+ T cells with a CD49dlo phenotype, CD8+ T cells with a CD49dlo CD44hi phenotype, or CD49dloCD44lo phenotype