The curious immune cells stuck between worlds

The problem is that scientists still don’t know much about how this unique type of T cell works and develops in humans. Hannah Meyer, an assistant professor at Cold Spring Harbor Laboratory (CSHL), and her collaborator at the University of Colorado at Anschutz, Professor Laurent Gapin, set out to determine precisely this phenomenon.

“Studying the development of the immune system is as important as studying its role in disease,” says Salomé Carcy, a former graduate student in the Meyer lab who co-led the study. “We need to understand the origin of immune cells to better understand their functional potential in disease contexts. A major motivation for our work was to determine how our knowledge gained from mouse models applies to human physiology.”

The team discovered that innate T cells mature differently in humans and mice, and that age plays a key role here. They found that early in life, most innate T cells in the human thymus are not able to use their full immune capabilities. It is as if they have one hand tied behind their back. In the blood of adults, however, it is a different story. There, innate T cells are on standby, ready to fight as soon as they receive their “go” signal. This pattern is observed in both mice and humans.

Meyer says these differences should be taken into account when developing and testing immunotherapies, especially since most preclinical trials are conducted in mouse models. “We need to take these differences into account,” Meyer says. “We would be interested in studying these differences to see how they evolve over time and whether these cells are more potent at different ages. And is that something we can exploit therapeutically?”

For now, Meyer and his team continue to unpack the complex lives of immune system agents such as innate T cells. Their work could one day allow researchers to harness the power of the innate and adaptive immune systems in a new, more formidable type of immunotherapy.