The focus of our work has been to develop specific immune-based approaches to investigate the regulation of autoimmunity by understanding the molecular, cellular and genetic basis of the regulatory T cell-mediated immune responses. Towards this goal we have investigated and reviewed the mechanism of disease prevention and islet tissue regeneration in autoimmune type 1 diabetes and the role that autoantigenic peptides, microbes and infections play in shaping our immune system at the T cell level.