Regulatory T Cell-Based Adoptive Cell Therapy in Autoimmunity

Regulatory T cells (Tregs) are a distinctive subset of CD4⁺ T cells critical in self-tolerance maintenance to prevent the development of autoimmunity. The mechanisms by which these cells provide immune regulation are numerous and, consequently, deeply involved in the pathogenesis of many autoimmune disorders. Treg-based adoptive cell transfer (ACT) therapy has generated interest as a novel, promising strategy to restore self-tolerance in autoimmunity. Polyclonal Treg-based ACT therapy was first implemented in clinical trials, presenting adequate safety profiles. Subsequent preclinical studies have shown antigen-specific Tregs to be safer and more effective than polyclonal approaches, so research has recently moved in this direction. Antigen-specificity can be conferred to Tregs by viral transduction of genes coding for engineered T cell receptors (eTCRs) or chimeric antigen receptors (CARs), with encouraging outcomes in different animal models of autoimmunity. This review focuses on the biology of Tregs, as well as on current preclinical and clinical data for Treg-based ACT in the field of autoimmunity.