What are the key immune mechanisms underlying transplant tolerance, and which novel strategies show promise for clinically safe rejection prevention?

Despite the continuous progress of immunosuppressants, long-term transplant rejection and drug toxicity remain major challenges. Transplant tolerance (a donor specific immune non responsive state that does not rely on sustained immune suppression) remains a difficult goal to achieve. The key mechanisms include central and peripheral immune regulation (such as regulatory T cells, immune exhaustion, clonal clearance, myeloid suppressor cells, etc.). The new strategies include co stimulatory signal blockade, regulatory cell therapy, chimeric induction, and tolerance promoting biomaterials. Please ask experts to clarify which mechanisms and pathways have the greatest clinical translational potential, and which combination therapies can safely achieve long-lasting tolerance in humans.