St. Jude and Emory University research shines a new light on T cell origins for drug development.

Researchers at St. Jude Children’s Research Hospital and Emory University recently conducted research that sheds new light on the origin of memory CD8 T cells.

Essential for long-term immune protection, hospital and university researchers explained that understanding white blood cells’ origins should help them understand and leverage these immune-system soldiers to help prevent or cure disease. The complementary studies of research in mice and humans were published in the journal, Nature. Researchers explained that the studies were intended to address the long-standing debate about memory cell origins.

Ben Youngblood, an Assistant Member of the St. Jude Department of Immunology, noted: “This research provides the most compelling evidence yet that memory CD8 T cells arise from effector CD8 T cells and, in fact, must transit through an effector stage of differentiation before becoming memory cells.” Youngblood was the lead and corresponding author of the primary study and co-author of related research appearing in Nature. Professor Rafi Ahmed, who serves in the Department of Microbiology and Immunology at Emory, was the co-corresponding author for both papers.

According to the study’s authors, effector CD8 T cells combat viral infections, cancer and other disorders and disease. In contrast, memory CD8 T cells function like sentries that circulate throughout the body, able to recognize and respond to the threats. Before these studies were conducted, scientists thought effector and memory T cells developed distinct lineages from naïve T cells.

Because Naïve T cells are less differentiated they are able to fashion themselves in response to novel viruses and other threats confronted by the immune system. Working with virally infected mice, Youngblood and his colleagues demonstrated how memory CD8 T cells are generated from a small subset of effector CD8 T cells.

The analysis by Youngblood and his colleagues included epigenetic and gene expression data as well as analysis of next-generation whole genome bisulfide sequencing, which captures DNA methylation. DNA methylation helps regulate gene expression. Tagging DNA with a methyl group can repress gene expression. Removing the methyl group, a process known as demethylation, allows the gene to be switched on.

The investigators explained memory that CD8 T cells retain epigenetic traces from their time as effector cells and that “app” is still available to fight infections even when transferred to another mouse. Through gene expression, knockout and similar methods, researchers demonstrated effector cells that become memory CD8 T cells undergo demethylation. “That allows,” said researchers, “the cells destined to become memory CD8 T cells to express genes associated with naïve T cells and transition from effector to memory T cells.”