Defining the molecular mechanisms underlying immunological memory in T cells (expression). Mus musculus

Immunological memory is a defining feature of animal development, allowing rapid responses to repeat infections, yet the very basis of T cell-dependent memory remains poorly understood. Here we demonstrate that the critical steps in the acquisition of T cell memory occur not after completion of T cell differentiation but during the initial activation phase of naïve T cells, when extensive chromatin remodelling reprograms immune response genes towards a stably maintained primed state. During this process, inducible factors including AP-1 create hundreds of DNase I hypersensitive sites (DHSs), allowing the recruitment of ETS1 and RUNX1 to sites that were previously inaccessible. Significantly, these DHSs remain temporally and mitotically stable long after cessation of AP-1 activation, and function to maintain regions of active chromatin in the vicinity of genes that regulate immune responses. This priming enables increased accessibility and the accelerated induction of other inducible regulatory elements in previously activated T cells. Overall design: Examination of gene expression patterns in naïve, blast, memory T-cells with or without PMA activation via microarray study.