Rapid Recall Ability of Memory T cells is Encoded in their Epigenome

Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naive and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the naive cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting naive, central and effector memory T cells using ChIP-Seq and found that unlike the naive cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory.