SRA

Memory CD8 T cells have a unique ability to provide lifelong immunity against pathogens. Although memory features generally arise after a challenge with foreign antigen, naïve CD8 single positive (SP) thymocytes may already acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these “innate memory” CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming was secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, we identified direct interaction between EOMES and BRG1 and showed that in vivo acquisition of EOMES-dependent program by CD8SP thymocytes was dependent on this chromatin remodeling factor. In conclusion, our results support a strong epigenetic basis for EOMES-driven establishment of CD8 T cell unconventional memory program. Overall design: CD8SP thymocytes: Innate Memory, Naïve, WT, and Eomes-TG