Restoration of self-tolerance is a feasible approach to control ongoing beta-cell specific autoreactivity: its relevance for treatment in establisheddiabetes and islet transplantation

Major progress has been made over the last 10 years in understanding the im mune mechanisms underlying autoimmune Type I (insulin-dependent) diabetes m ellitus. It seems that immunotherapy is the best approach for preventing an d/or arresting beta cell destruction. For immunotherapeutic approaches to b e clinically applicable to Type I diabetes, they cannot rely on the use of non-specific immunosuppressants. Their relative ineffectiveness over the lo ng term and the risk of recurrence, once the drug is withdrawn, requires pe rmanent drug treatment which augments problems of infection and drug toxici ty. One solution is to selectively tackle the pathogenic immune response. O perationally, this requires establishing immunological tolerance, i.e. a st ate of durable antigen-specific unresponsiveness in the absence of generali sed immunosuppression. This review aims to present the rationale and clinic al applicability of possible immunointervention strategies in Type I diabet es aimed at restoring self-tolerance to beta cells.