Immune Cells Turn Back Time to Achieve Memory

Source: Emory University

Summary: Researchers have found a new mechanism in the memory of immune system which helps the body remember what infections or vaccines someone has been exposed to.

Memory T cells are a subset infection-fighting T cells which circulate in the blood. They earn their name by embodying the memory of the immune system. To become memory T cells, they go backward in time, relinquishing their status as immune foot soldiers. The trained memory CD8 T cells kill the cells that are infected by a virus or which do not belong to the body. What distinguishes memory CD8 T cells from untrained naive cells is that they can respond rapidly, within minutes or hours. The new research illuminates how they do it – their genes are poised to respond, even years after initial activation. Researchers from the Emory University came to that conclusion by tracking the patterns of gene expression and DNA methylation in memory CD8 T cells, and comparing them with naive CD8 T cells and effector (foot soldier) cells. The study findings were published in the journal Nature.

Trained memory CD8 T cells kill the cells that are infected by a virus

Scanning Electron Micrograph of Human T Cells (orange). Credit: MSKCC

Researchers used heavy water labeling technique to follow the immune cells over time. In this technique, deuterium is incorporated into every newly synthesized DNA or protein, occurring during cell division. To address the question, whether the memory T cells develop from effector cells or directly from a subset of naive cells researchers looked at genes that are turned on in naive cells, off in effector cells, and then on again in memory cells. They found that memory precursor cells re-express genes such as L-selectin (an adhesion molecule needed for immune cells to home to lymph nodes) and this shift is accomplished by erasing previously acquired DNA methylation (is an epigenetic modification – usually turns off genes) on those genes.

Asst. Prof. Rama Akondy said, “We think memory CD8 T cells retain an ‘epigenetic signature’ of having transitioned through the effector state”, “The effector genes stay unmethylated and are poised to be re-activated.”

Director of Emory Vaccine Center, Dr. Rafi Ahmed said, “the findings could be also relevant for memory CD4 T cells, a major reservoir for HIV persistence. Understanding how memory CD4 T cells re-activate could aid efforts to eliminate HIV from the body”.

More Information: Ben Youngblood et al, “Effector CD8 T cells dedifferentiate into long-lived memory cells”, Nature (2017).DOI: 10.1038/nature25144

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