For the immune system to effectively fight pathogens, antibody responses must be precisely controlled. So-called follicular regulatory T cells (Tfr cells) play a key role in this process by limiting excessive immune responses and helping maintain immune tolerance. Researchers at the University Hospital Bonn (UKB) and the University of Bonn have developed a powerful experimental method that allows them to generate Tfr cells from progenitor cells and study them in a targeted manner. The results were recently published in the journal Cellular & Molecular Immunology.
Tfr cells control the development and function of so-called germinal centers in lymphoid organs such as lymph nodes, tonsils, and spleen. There, it modulates the activity of follicular helper T cells (Tfh cells) and B cells, allowing antibody responses to remain effective without going out of control. An imbalance between activated and regulatory immune cells is associated with autoimmune diseases and misdirected antibody responses.
Tfr cells have traditionally been difficult to study. Using our model, we can now specifically follow their development in the laboratory and investigate the molecular mechanisms that control their properties and functions. ”
Dr. Luisa Bach, first author, scientist, Bonn University Hospital
How follicular regulatory T cells develop
For the study, the scientists developed a new in vitro model that can generate Tfr cells from specific CD4+ T helper cells of the immune system. Using this system, they were able to identify key molecular signaling pathways that control the development of these cells.
The growth factor TGF-β was found to play an important role. This is necessary and sufficient to trigger the characteristic program of Tfr cells. At the same time, the signaling molecule IL-2 influences cell development in the opposite way. Only a finely tuned interaction of both signaling pathways allows the formation of functional Tfr cells.
Additionally, the researchers identified the transcription factor c-Maf as a key regulator of Tfr cell differentiation. In the absence of this factor, the cells are unable to fully develop the characteristics typical of Tfr cells.
Laboratory-proven control of antibody responses
The researchers were also able to show that laboratory-generated Tfr cells are functionally similar to natural Tfr cells. In cell culture experiments, we suppressed Tfh cell-mediated B cell activation and limited the formation of specific classes of antibodies.
“Tfr cells are one of the most important regulators of antibody responses. The fact that their distinctive properties can now be investigated specifically in cell culture opens new possibilities for the study of their biological functions,” explains corresponding author Professor Dirk Baumjohan from the UKB Department of Hematology, Oncology, Immuno-Oncology and Rheumatology. He is also a member of the steering committee of the Cluster of Excellence Immunosensation 3 and the Interdisciplinary Research Area. (TRA) “Life and Health” at the University of Bonn. “This will allow us to better understand how antibody responses are regulated and how spurious immune responses can occur.”
New tools for immunology research
This study provides fundamental insights into the biology of regulatory immune cells while providing an important tool for immunological research. The newly developed model will allow researchers to specifically investigate the development and function of Tfr cells and dissect their role in immune responses in more detail.
sauce:
Bonn University Hospital (UKB)
Reference magazines:
Bach, L. others. (2026) TGF-β and IL-2 differentially shape T follicle regulatory cell differentiation and stability in vitro. Cellular and molecular immunology. DOI: 10.1038/s41423-026-01440-9. https://www.nature.com/articles/s41423-026-01440-9
