BONN — Researchers at the University Hospital Bonn and the University of Bonn developed a laboratory method to generate follicular regulatory T cells (Tfr cells) from precursor cells. The findings were published in the journal Cellular & Molecular Immunology on June 25, 2026.

The scientists developed an in vitro model that allows Tfr cells to be generated from CD4+ T helper cells. They identified key molecular signaling pathways that control the development of Tfr cells.

The growth factor TGF-β is necessary and sufficient to trigger the characteristic program of Tfr cells. The signaling molecule IL-2 influences the development of Tfr cells in an opposing manner to TGF-β. The interaction of TGF-β and IL-2 signaling pathways enables the formation of functional Tfr cells.

The research team identified the transcription factor c-Maf as a regulator of Tfr cell differentiation. Tfr cells cannot fully develop their typical characteristics if c-Maf is absent.

The Tfr cells generated in the laboratory function similarly to natural Tfr cells. In cell culture experiments, the generated Tfr cells suppressed Tfh-cell-mediated activation of B cells. They also limited the formation of certain antibody classes.

"With our model, we can now specifically track their development in the laboratory and investigate the molecular mechanisms that control their properties and functions," said Dr. Luisa Bach, a scientist at University Hospital Bonn.

"Tfr cells are among the most important regulators of the antibody response," said Prof. Dirk Baumjohann from the Department of Hematology, Oncology, Immuno-Oncology, and Rheumatology at University Hospital Bonn. "The fact that their characteristic properties can now be specifically investigated in cell cultures opens up new possibilities for researching their biological function."

Why It Matters

Follicular regulatory T cells limit excessive immune responses and help maintain immune tolerance. They control the development and function of germinal centers in lymphoid organs such as lymph nodes, tonsils, and the spleen. Moreover, Tfr cells regulate the activity of follicular T helper cells and B cells. An imbalance between activating and regulatory immune cells is associated with autoimmune diseases and misdirected antibody responses.