Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells

CD8+ T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8+ T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of ‘virtual memory’ CD8+ T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of ‘virtual memory’ CD8+ T cells in an Eomes-dependent fashion. We further show that the development of ‘innate thymic’ CD8+ T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8+ T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8+ T cells.