by Osaka University

(a) Effector Tregs (eTregs) most strongly affect CD8-EM cells and B-plasma cells. (b) A closer look reveals eTregs control CD8-EM cells by stopping their division and reducing GzmB while maintaining CD27. (c) Dividing eTregs increase CD98, GLUT1, and CTLA4 proteins, and shows how an anti-CTLA4 antibody affects this process. (d) Reveals a potential biomarker by showing two distinct types of eTregs: one expressing HLA-DR and CCR4, and another expressing CD38 and CCR7 - a pattern seen in severe viral infections. (e) Ranks different Treg types by their suppressive ability, with eTregs being strongest. (f) Demonstrates how the drug Tazemetostat blocks naive Tregs from becoming eTregs during early cell division. Credit: 2025 Søndergaard et al., Single cell suppression profiling of human regulatory T cells., Nature Communications

Developing effective treatments and understanding how the mechanism of the immune system have always been challenging for scientists. T cells, which are the frontline warriors in the battle against infections, have been a major focus of research.

Regulatory T cells (Tregs) are specialized immune cells that have a challenging task in the body. They must balance the immune system by making it aggressive enough to fight infection and cancer but calm enough not to attack the body's normal cells. Tregs meet this challenge by controlling the actions of other immune cells. However, we don't know exactly how these cells interact during disease and treatment.

In a study recently published in Nature Communications, a research team at Osaka University has developed a new technique that reveals how Tregs exert their control. The new technique, called single-cell suppressive profiling of regulatory T cells (scSPOT), can pinpoint the effects of Tregs on all other immune cells simultaneously. Previously, researchers could only observe interactions between one or two cell types at a time.

"This new method provides a better understanding of how Tregs function in a complex immune environment in a way that closely resembles what happens in the human body," explains first author of the study Jonas Nørskov Søndergaard. "Using scSPOT, we found that Tregs most strongly affect CD8-EM T cells by suppressing their ability to grow and divide."

CD8-EM T cells are a subset of memory T cells that have a key role in fighting cancer and infections, highlighting how Tregs are closely tied with health and disease. The team also found that Tregs are targets for the cancer drugs ipilimumab and tazemetostat, although the two drugs affect Tregs in different ways. Tregs are indicators of serious viral infection too, since scSPOT identified special types of Tregs like the ones seen in patients with severe COVID-19 infection.

"Our new scSPOT method is a valuable tool that may accelerate the development of treatments for cancer and other diseases," says senior author James Wing. "In particular, the discovery of indicators of severe viral infections may allow health care professionals to identify high-risk patients earlier, allowing for faster treatment during outbreaks and pandemics."

The team's scSPOT method has already boosted our understanding of the immune system. The insights it provides into the ways existing drugs work could help investigators develop more effective treatment strategies, leading to better outcomes for patients.

More information: Jonas Nørskov Søndergaard et al, Single cell suppression profiling of human regulatory T cells, Nature Communications (2025). DOI: 10.1038/s41467-024-55746-1

Journal information: Nature Communications 

Provided by Osaka University