Super excited to see Luisa’s work on in vitro differentiation of Tfr cells now published in Cellular & Molecular Immunology (Open Access):
TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro
Bach L, Chang Y, Arteaga Transito O, Ghasemi M, Steinheuer LM, Steffen T, De Domenico E, Ulas T, Wunderlich FT, Beyer MD, Thurley K, Baumjohann D.
Cell Mol Immunol. 2026 Jun 25. doi: 10.1038/s41423-026-01440-9.
Abstract: T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells play critical roles in regulating the activity of the germinal center (GC), which is essential for the generation of high-affinity antibodies. In the GC, Tfh cells help B cells to proliferate and to differentiate into memory B cells and long-lived plasma cells. In contrast, Tfr cells, a specialized subset of regulatory T cells (Tregs), modulate the humoral immune response by suppressing excessive or autoreactive B-cell activity. Here, we established an in vitro differentiation protocol for mouse CD4⁺ T cells that yielded CXCR5⁺FoxP3⁺ Tfr cells that exhibited a Bcl6hiPD-1hiCD25loGITRint phenotype and were distinct from Treg and Tfh cells. Functionally, in vitro-generated Tfr cells potently suppressed Tfh cell-driven B-cell class switching to IgG1 and downregulated the expression of B-cell costimulatory ligands. While in vitro-generated Bcl6-deficient Tfh cells were impaired in providing help to B cells for efficient class switching to IgG1, in vitro-generated Bcl6-deficient Tfr cells failed to inhibit Tfh cell-driven B-cell class switching to IgG1. Mechanistically, we showed that Tfr cells emerged from FoxP3+ precursors in low-IL-2 environments through a TGF-β- and c-Maf-dependent pathway, allowing for reprogramming and reinforcement of the follicular regulatory cell program in CD4+ T cells in vitro.
Congratulations to her and all the team members and collaborators!