Well-thumbed references often contain “dog ears,” folded down corners of book pages that mark off selected passages. These dog ears create extra spaces between the pages of a closed book so that it when it opens, it will reveal important passages without delay.

Something like that happens in the chromatin of immune cells. Chromatin, which packages genetic information, is the ultimate reference work, and immune cells consult it when they encounter infections and need to recall how to handle them.

While immune cells are known to rely on immunological memory, the molecular details are still hazy. In the hope of clearing things up, scientists based at the University of Birmingham studied how T cells were affected by an antigenic stimulus. The scientists found that during initial activation, the chromatin of naïve T cells underwent extensive remodeling. This remodeling, or epigenetic imprinting, reprogrammed immune response genes toward a stably maintained primed state.

According to the scientists, who were led by Professor Peter Cockerill, epigenetic imprinting occurs at the genes that need to be switched back on as soon as immune cells are reactivated. They propose that this forms the basis of a long-term memory that allows for an immediate response when the body encounters an infection and T cells are activated for a second time.

The details of this work appeared January 21 in The EMBO Journal in an article entitled “Inducible chromatin priming is associated with the establishment of immunological memory in T cells.”

“Activation induced the transcription factors NFAT and AP-1, which created thousands of new DNase I-hypersensitive sites (DHSs), enabling ETS-1 and RUNX1 recruitment to previously inaccessible sites,” wrote the article’s authors. “Significantly, these DHSs remained stable long after activation ceased, were preserved following replication, and were maintained in memory-phenotype cells.”

Rather than  remain “switched on” permanently to fight infection continuously, the immune cells return to a dormant state—but they are altered by the initial infection and remain in a partially active state primed to combat any recurrence.

Professor Cockerill explained, “The initial immune response switches on certain regions within chromosomes of previously inactive T cells to leave them in a more open structure so that they can then sit poised, ready to respond much faster when activated again in the future.”

Being able to silence the immune system until it is required to fight infection is also vitally important, else there would be a risk of damaging cells that are part of the host. The team identified a mechanism that allows cells to remain poised without producing the molecules associated with inflammation that are used to fight infection. If this tight control breaks down and healthy cells are targeted as if they were foreign, it can be the cause of a number of inflammatory or autoimmune disorders.

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