Immunological Tolerance: Therapeutic Induction

When the natural mechanisms of immune tolerance break down, autoimmune or allergic disease can result. There is considerable experimental evidence that the ultimate response to antigen, full immunity or tolerance, is dependent on the activation status of the antigen-presenting dendritic cells, with those in steady state inducing tolerance. Current therapeutic options either deplete immune cell populations, interfere with immune cell trafficking to the tissues or inhibit inflammatory cytokine function or lymphocyte signalling. Although these treatments can be effective for certain diseases, they carry with them significant adverse effects and it is unlikely that they induce true, long-lived immune tolerance. Cellular therapies using either tolerogenic dendritic cells or regulatory T cells may be able to achieve this. Alternatively, administration of antigen in tolerogenic form can provide the most specific therapy, with the least risk of adversely affecting normal immune function against infection or neoplasia.