Figuring out how T cells interpret signals

Cytokines are small proteins that convey signals among immune system cells. St. Jude scientists are studying how cytokines that promote inflammatory responses affect T cells.

This work showed how T cells tailor their response based on signals from other immune cells. The team found that cytokine IL-12 signaling works through a factor called TET2. This factor tells CD8 T cells how to enhance their response toward pathogens and tumors.

“We now have a better idea about the rules that govern epigenetic control of a T-cell response,” said Benjamin Youngblood, PhD, St. Jude Department of Immunology. “We looked at how signals used during the activation and expansion of T cells change the cells in a long-lived manner.

“You can modify the T cells by just culturing them with the right cytokine for a few days,” he said. “It will have a long-term impact.”

The results show that cytokines can be used to guide CAR T–cell therapy.

“When we're thinking about making CAR T–cells, our work provides a framework for selecting specific cytokines in the manufacturing process that can induce desired epigenetic programs,” said Caitlin Zebley, MD, PhD, St. Jude Department of Bone Marrow Transplantation and Cellular Therapy.

Cell Reports published this work.