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Technologies that induce antigen-specific immune tolerance by mimicking naturally occurring mechanisms have the potential to revolutionize the treatment of many immune-mediated pathologies such as autoimmunity, allograft rejection, and allergy. The immune system intrinsically has central and peripheral tolerance pathways for eliminating or modulating antigen-specific responses, which are being exploited through emerging technologies. Antigen-specific tolerogenic responses have been achieved through the functional reprogramming of antigen-presenting cells or lymphocytes. Alternatively, immune privileged sites have been mimicked using biomaterial scaffolds to locally suppress immune responses and promote long-term allograft survival. This review describes natural mechanisms of peripheral tolerance induction and the various technologies being developed to achieve antigen-specific immune …