Inducing immune tolerance: a focus on Type 1 diabetes mellitus

    loading  Checking for direct PDF access through Ovid



Tolerogenic strategies that specifically target diabetogenic immune cells in the absence of complications of immunosuppression are the desired treatment for the prevention or even reversal of Type 1 diabetes (T1D). Antigen (Ag)-based therapies must not only suppress disease-initiating diabetogenic T cells that are already activated, but, more importantly, prevent activation of naive auto-Ag-specific T cells that may become autoreactive through epitope spreading as a result of Ag liberation from damaged islet cells. Therefore, identification of auto-Ags relevant to T1D initiation and progression is critical to the design of effective Ag-specific therapies. Animal models of T1D have been successfully employed to identify potential diabetogenic Ags, and have further facilitated translation of Ag-specific tolerance strategies into human clinical trials. In this review, we highlight important advances using animal models in Ag-specific T1D immunotherapies, and the application of the preclinical findings to human subjects. We provide an up-to-date overview of the strengths and weaknesses of various tolerance-inducing strategies, including infusion of soluble Ags/peptides by various routes of delivery, genetic vaccinations, cell- and inert particle-based tolerogenic approaches, and various other strategies that target distinct tolerance-inducing pathways.

Related Topics

    loading  Loading Related Articles