Dr Kristine Hardy, Biomedical Sciences, Faculty of Education, Science, Technology & Maths, University of Canberra.
Naive T cells exist in a resting state until activated by the antigen they are specific for. Upon activation, T cells produce cytokines and other proteins necessary to fight infections and proliferate to produce more T cells specific for that antigen. Some of these descendants will be long-lived memory T cells, which will return to a resting state but are primed for a more rapid and robust immune response upon re-exposure to the same antigen. Using a T lymphocyte cell culture model of transcriptional memory we have investigated the possibility that previously stimulated cells have differences in DNA accessibility compared to non-stimulated cells. We used Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) in conjunction with high throughput sequencing to identify changes in DNA accessibility in response to stimulation, resting and re-stimulation. We found that although many of the changes in accessibility that were induced upon stimulation, were reversed upon stimulus withdrawal and resting of the cells, a large proportion remain accessible and a subset of these are near genes that have enhanced induction upon re-stimulation. Interestingly the accessibility associated with these memory-responsive genes was not always at the transcription start site but sometimes occurred in putative enhancers of these genes. Characterisation of these sites suggests that different transcription factor families have differing roles for creating and maintaining accessibility.