Epigenetic changes to the chromatin of memory T cells allow them to respond rapidly to re-infection
As we slowly emerge from the cold and flu season, pockets filled with tissues and bottles of hand sanitizer, the thought of a way to defeat these elusive viruses is never more attractive. Perhaps that’s why a group of researchers at the University of Birmingham, UK, have explored the “immunological memory” that allows our immune systems to respond quickly to re-stimulation by a pathogen. As a result of this exploration, the team has discovered a new class of gene regulatory elements that imprint on the chromosomes of T cells, keeping the chromatin in its “active” conformation and ensuring that the cells can respond quickly to threats they’ve seen before (1).
It has been known for many years that recently activated T cells respond much faster to re-stimulation than naïve or immature T cells. We also know that these recently activated T cells acquire a different pattern of epigenetic modifications in the active regions of chromatin at gene regulatory elements. “When we put these two facts together,” says Peter Cockerill, who led the team that made the discovery, “we realized that it was the epigenetic priming of cells that allowed them to respond much faster, and we saw that this had the potential to at least partly account for the increased immune response after vaccination or infection.”
Immune memory involves both an expansion of the T and B cells that recognize a specific pathogen, and those cells’ enhanced ability to respond to the same pathogen again. What the Birmingham researchers found is that one cycle of T cell receptor activation is sufficient to reprogram the genome by introducing “hotspots” that make specific chromosome regions more accessible. Upon closer inspection, Cockerill explains, it turned out that these regions encompassed the inducible transcriptional enhancers that regulate immune response genes – so the priming mechanism is a simple way to make hundreds of genes respond much faster.
The discovery may have implications not just for fighting infections, but also in autoimmune diseases. “You would expect to find autoimmune and inflammatory disorders associated with a higher proportion of ‘memory-like’ T cells,” says Cockerill. Such diseases are also associated with excessive cytokine production. “We could aim to target the pathways that keep these regions open, which may involve these pro-inflammatory cytokines and the kinase signalling pathways linked to them. This is similar to what is already being done with anti-TNF therapy in rheumatoid arthritis, where the cytokine network is targeted at one key point.”
Cockerill and his colleagues have uncovered part of the explanation for how immunity is acquired, and why naïve and memory T cells behave differently. “We identified the first stage of this process which is the establishment of epigenetic priming in direct response to T cell activation.” But where will their research go next? “We know that immunity lasts for decades, and circulating memory T cells have the same modification patterns as recently activated T cells”, he says. “The search is now on for the mechanisms that allow epigenetic priming to become re-established after each cell division, and to be maintained for years when these cells stop dividing.”
- SL Bevington et al., “Inducible chromatin priming is associated with the establishment of immunological memory in T cells”, EMBO J, [Epub ahead of print] (2016). PMID: 26796577.
While obtaining degrees in biology from the University of Alberta and biochemistry from Penn State College of Medicine, I worked as a freelance science and medical writer. I was able to hone my skills in research, presentation and scientific writing by assembling grants and journal articles, speaking at international conferences, and consulting on topics ranging from medical education to comic book science. As much as I’ve enjoyed designing new bacteria and plausible superheroes, though, I’m more pleased than ever to be at Texere, using my writing and editing skills to create great content for a professional audience.