Limited sustainability of regulatory T cell repertoire revealed by novel genetic switches 2257672

Introduction Regulatory T (Treg) cells carry a diverse T-cell antigen receptor (TCR) repertoire, playing a crucial role in suppressing inflammatory T cells reactive to self-antigens and innocuous foreign antigens. Despite their long lifespan, questions arise about how the diverse Treg repertoire is faithfully sustained during extended antigen stimulation. Methods In this study, we employ a novel genetic approach to demonstrate that Treg cells possess substantial stemness for self-renewal in native physiological conditions. Results The suppressive capacity of existing Treg cells declines over time, leading to impaired fitness and stability. Timestamp tracing further reveals constant thymic Treg development and influx into the peripheral Treg pool, which is essential for maintaining the integrity of Treg repertoire. Conclusion These findings demonstrate the limited sustainability of Treg repertoire, providing valuable guidance for Treg-based treatment of autoimmune disease.