Prevention of autoimmune type 1 diabetes via mucosal tolerance: is mucosal autoantigen administration as safe and effective as it should be?

Abstract

Mucosal immune response to an antigen leads to a state of attenuated systemic response to the same antigen, known as mucosal or oral tolerance. Thus, autoantigen administration via mucosal routes could be useful in the prevention of autoimmune diseases. Although in various models of autoimmune disease it is often effective, in some cases it is ineffective and in other cases even harmful. In these cases it is likely that, concomitantly with tolerance, a productive immune response is induced that exacerbates autoimmunity. Recent evidence suggests that induction of cytotoxic T lymphocytes capable of destroying pancreatic beta cells may be an unavoidable consequence of mucosal administration of pancreatic beta-cell associated autoantigen. To improve the safety and efficacy of mucosal tolerance induction in the prevention of type 1 diabetes, further means to control the induction of cytotoxic T lymphocytes and other potentially tissue-destructive immune effectors may be required.