Immunological Tolerance: Therapeutic Induction

Immunological tolerance can be defined as an unresponsiveness of T and/or B cells to self antigens. Low responsiveness of T cells and/or B cells to self antigens could be termed partial tolerance. Protection from the development of autoimmune diseases and acceptance of transplanted organs or tissue are due to effective tolerance to self antigens and alloantigens, respectively. The breakdown of tolerance to self antigens, due to mechanisms that are still obscure, culminates in the development of autoimmune diseases. It has been suggested that tolerance to self antigens occurs by clonal deletion, anergy, ignorance and/or suppression by so-called regulator cells and the cytokine(s) they secrete (e.g. transforming growth factor b, TGFb). Also, deviation from pathogenic to nonpathogenic Tand/or B-cell responses to self antigens could induce tolerance to pathogenic Tand/or B-cell responses. The therapeutic induction of tolerance is indicated in the treatment or prevention of autoimmune diseases and in the prevention of transplanted organ or tissue rejection. The ultimate goal is to induce self antigenspecific or alloantigen-specific tolerance to cure autoimmune diseases or prevent graft rejection, respectively. However, nonself antigen-specific or nonalloantigenspecific tolerancewithminimal global immunosuppression and toxicity could also be effective in ameliorating autoimmune diseases or preventing graft rejection. This review will discuss the various strategies for therapeutic induction of tolerance and the possible mechanisms involved in animal models of autoimmune diseases and transplantation.