Abstract
Even though T-cell receptor (TCR) stimulation together 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. Here, we 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 propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory.
Highlights
Long-lived memory T cells form the basis of adaptive immunity by orchestrating memory immune response
To examine whether the differential induction of cytokine genes between the CD4 T cell subsets is related to their epigenetic landscapes, we used ChIP-Seq to analyze genome-wide distribution of four positive chromatin marks and RNA Polymerase II (Figs 1 and 2 and S2 and S3)
We demonstrate that the cytokine genes integral to T cell function and protective immunity are “poised” and ready for rapid induction in memory T cells
Summary
Long-lived memory T cells form the basis of adaptive immunity by orchestrating memory immune response. As reported by Lai et al.[10] in a murine model of immunity against influenza, NF-κB is activated and translocates to the nucleus at similar levels in both naïve and memory T cells but is only able to bind DNA and induce expression of Ifng in memory T cells These findings suggest that rapid recall ability is mediated by the ability of transcription factors to bind to DNA at the appropriate genes, which is in turn regulated epigenetically by the local chromatin state. The appearance of positive chromatin marks at the promoters and/or enhancers of genes upon differentiation of naïve T cells to TCM or TEM may lead to increased expression level of the genes in resting cells and to increased inducibility of these genes upon activation, whereas loss of positive marks correlated with the loss of inducibility These results support the hypothesis that the rapid recall ability of memory T cells is encoded in their epigenome
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