IMMUNOLOGY2025™ Conference Recordings-Tolerance induction with engineered Tregs

Video Transcription

Video Summary

The speaker discusses regulatory T-cell (Treg) therapy, focusing on engineered CAR Tregs as a way to induce long-lasting immune tolerance. While much of the lab’s broader work involves human Tregs, the talk presents mouse studies to explore mechanisms and clinical potential.<br /><br />A major theme is “infectious tolerance,” where Tregs not only suppress effector cells but can also convert them into new Tregs, potentially creating durable immune regulation. The speaker highlights CAR Tregs engineered to recognize HLA-A2, a common transplant mismatch antigen. In transplantation models, these cells homed specifically to A2-positive grafts, prolonged graft survival, and showed stronger effects than polyclonal Tregs.<br /><br />The talk then extends CAR Treg function beyond alloimmunity into autoimmunity using an islet transplantation model. A2 CAR Tregs suppressed diabetogenic T cells, reduced inflammation in both graft and native pancreas, lowered inflammatory cytokines, and promoted conversion of pathogenic T cells into FOXP3+ regulatory cells. Even after CAR Tregs were removed, tolerance persisted, supporting infectious tolerance.<br /><br />Finally, in a fully immunocompetent heart transplant model, CAR Tregs combined with CD40 ligand blockade improved graft acceptance and induced tolerance to multiple indirect alloantigens, including T- and B-cell responses. The speaker concludes that CAR Tregs can mediate linked suppression and infectious tolerance, with strong promise for transplantation and autoimmune disease therapy.

Keywords

regulatory T-cell therapy

CAR Tregs

infectious tolerance

HLA-A2

transplantation tolerance

FOXP3+ regulatory cells

autoimmunity