Researchers at the University Hospital Bonn and the University of Bonn announced on June 25 that they have developed a laboratory method allowing follicular regulatory T cells, or Tfr cells, to be generated from precursor cells and studied in a targeted manner. The findings were published in the journal Cellular & Molecular Immunology.
Tfr cells play a crucial role in controlling antibody responses by regulating germinal centers within lymphoid organs such as lymph nodes, tonsils, and spleen. In these centers, Tfr cells help balance the activity of follicular T helper cells and B cells to ensure effective but controlled immune responses. An imbalance between activating and regulatory immune cells is linked to autoimmune diseases and improper antibody reactions.
The research team created an in vitro model that generates Tfr cells from specific CD4+ T helper cell populations. This system enabled identification of key molecular signaling pathways involved in the development of these regulatory immune cells.
Their experiments showed that the growth factor TGF-β is both necessary and sufficient for initiating the characteristic program of Tfr cell development. Conversely, the signaling molecule IL-2 was found to influence this process in an opposing way. Only a finely tuned interaction between these two signaling pathways allows functional Tfr cell formation. Additionally, researchers identified c-Maf as an important transcription factor; without it, developing cells could not acquire typical characteristics of mature Tfr cells.
Laboratory-generated Tfr cells were functionally similar to their natural counterparts: they suppressed activation of B cells mediated by follicular helper T-cells and limited production of certain antibody classes during experiments.
"Tfr cells are among the most important regulators of the antibody response. The fact that their characteristic properties can now be specifically investigated in cell cultures opens up new possibilities for researching their biological function," said Prof. Dirk Baumjohann from UKB's Department of Hematology, Oncology, Immuno-Oncology, and Rheumatology at UKB. "This allows us to better understand how antibody responses are regulated and how misdirected immune reactions arise."
