Auto-antigen and Immunomodulatory Agent-Based Approaches for Antigen-Specific Tolerance in NOD Mice

Type 1 diabetes (T1D) can be managed by insulin replacement, but it is still associated with an increased risk of microvascular/cardiovascular complications. There is considerable interest in antigen-specific approaches for treating T1D due to their potential for a favorable risk-benefit ratio relative to non-specific immune-based treatments. Here we review recent antigen-specific tolerance approaches using auto-antigen and/or immunomodulatory agents in NOD mice and provide insight into seemingly contradictory findings.

Although delivery of auto-antigen alone can prevent T1D in NOD mice, this approach may be prone to inconsistent results and has not demonstrated an ability to reverse established T1D. Conversely, several approaches that promote presentation of auto-antigen in a tolerogenic context through cell/tissue targeting, delivery system properties, or the delivery of immunomodulatory agents have had success in reversing recent-onset T1D in NOD mice. While initial auto-antigen based approaches were unable to substantially influence T1D progression clinically, recent antigen-specific approaches have promising potential.