Model of FVIII-specific human CAR Treg function. Cartoon depicting suppressive function of FVIII-specific CAR-engineered human Tregs to FVIII-specific TCR-engineered T-effector cells or antibody-producing B cells in response to FVIII. FVIII-loaded APCs might bring T-effector cells and Tregs into close proximity. Thus, activated Tregs can inhibit T-effector cell activation in this local milieu (eg, by IL-2 consumption). Inhibition of T-effector cells also leads to prevention of FVIII inhibitor formation as costimulatory signals of T-effector cells are essential for B-cell activation. In addition, activated Tregs might influence B cells directly by still unknown mechanisms.