Even though T cell receptor (TCR) stimulation coupled with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage-specific cytokines much more rapidly than the naïve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. We have performed epigenetic profiling of human resting naïve, central and effector memory T cells using ChIP-Seq and found that unlike the naïve 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 are now aiming to prove the causal relationship between the presence of epigenetic marks and cytokine gene reproducibility. If successful, this project will allow for epigenetic reprogramming of T cell responses.
Chromatin Marks at the Th2 Cytokine Locus. (a) Human naïve and effector memory T (TEM) cells were isolated from blood and activated with anti-CD3/28 beads for 40 min, 150 min or 15 h. Expression of the cytokine genes, IL13 (a) and IL4 (c) was measured by RNA-Seq. ChIP-Seq profiles for active chromatin marks (H3K4me1, H3K4me3 and H2A.Z) are shown in resting cells (b). Putative regulatory elements are denoted on top. Gray boxes highlight the areas where epigenetic changes are observed.