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

Abstract

Purpose of Review

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.

Recent 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.

Summary

While initial auto-antigen based approaches were unable to substantially influence T1D progression clinically, recent antigen-specific approaches have promising potential.

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Fig. 1

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Acknowledgments

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Funding

E.J.B. was supported in part by a fellowship (T32-AI074490) from the NIH National Institute of Allergy and Infectious Diseases and the ARCS Foundation Scholar Award. The funders had no role in the decision to publish or the preparation of this manuscript.

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S.R.L. and J.D.P. are both corresponding authors for the manuscript. E.J.B. conceived of the review, and all authors contributed to writing and editing the manuscript.

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Correspondence to Ethan J. Bassin or Jon D. Piganelli or Steven R. Little.

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Conflict of Interest

Steven R. Little is an inventor on patent 14/372,977 entitled “Controlled Release Formulations for the Induction and Proliferation of Blood Cells” which was issued to the University of Pittsburgh on 04/30/20. This patent covers the TRI MP formulation discussed in this manuscript.

Ethan J. Bassin and Jon D. Piganelli each declare they have no competing interests.

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This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes

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Bassin, E.J., Piganelli, J.D. & Little, S.R. Auto-antigen and Immunomodulatory Agent–Based Approaches for Antigen-Specific Tolerance in NOD Mice. Curr Diab Rep 21, 9 (2021). https://doi.org/10.1007/s11892-021-01376-6

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Keywords

  • Type 1 diabetes (T1D)
  • Antigen-specific
  • Auto-antigen therapy
  • Tolerance
  • Non-obese diabetic (NOD) mice
  • Regulatory T cells (Tregs)