Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity

作者：Marco Romano, Giorgia Fanelli, Caraugh Jane Albany, Giulio Giganti, Giovanna Lombardi · 发表于：Frontiers in Immunology · 年份：2019 · DOI：10.3389/fimmu.2019.00043 · 被引用次数：513 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、CAR-T cell therapy research

Regulatory T cells (Tregs) are important for the induction and maintenance of peripheral tolerance therefore, they are key in preventing excessive immune responses and autoimmunity. In the last decades, several reports have been focussed on understanding the biology of Tregs and their mechanisms of action. Preclinical studies have demonstrated the ability of Tregs to delay/prevent graft rejection and to control autoimmune responses following adoptive transfer in vivo. Due to these promising results, Tregs have been extensively studied as a potential new tool for the prevention of graft rejection and/or the treatment of autoimmune diseases. Currently, solid organ transplantation remains the treatment of choice for end-stage organ failure. However, chronic rejection and the ensuing side effects of immunosuppressant represent the main limiting factors for organ acceptance and patient survival. Autoimmune disorders are chronic diseases caused by the breakdown of tolerance against self-antigens. This is triggered either by a numerical or functional Treg defect, or by the resistance of effector T cells to suppression. In this scenario, patients receiving high doses of immunosuppressant are left susceptible to life-threatening opportunistic infections and have increased risk of malignancies. In the last 10 years, a few phase I clinical trials aiming to investigate safety and feasibility of Treg-based therapy have been completed and published, while an increasing numbers of trials ar...