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Current Diabetes Reports

, Volume 12, Issue 5, pp 623–632 | Cite as

Autologous Regulatory T Cells for the Treatment of Type 1 Diabetes

  • James A. Thompson
  • Daniel Perry
  • Todd M. BruskoEmail author
Transplantation (A Pileggi, Section Editor)

Abstract

The immune system is tasked with defending the host from a wide array of pathogens and environmental insults. When uncontrolled, this endeavor may lead to off-target reactivity to self-tissues resulting in multiple autoimmune diseases including type 1 diabetes (T1D). This multifactorial disease process involves over 40 susceptibility genes and is influenced by poorly characterized environmental factors. While many questions regarding the pathogenesis of the disease process remain, it has become increasingly clear that the progression to disease results from a breakdown in the processes that maintain peripheral immune tolerance. The end result of this process is localized tissue inflammation, islet dysfunction, and ultimately the destruction of pancreatic β cells due to concomitant defects in innate and adaptive immune responses. A number of immunomodulatory intervention trials have now been conducted in patients at risk for or with recent onset T1D, often with the goal of restoring immune tolerance by inducing regulatory T cells (Tregs). Unfortunately, many of these trials have fallen short of inducing persistent immune regulation. This shortfall has led to additional efforts to more directly shift the balance from destructive effector T cell (Teff) responses to favor Tregs, including the use of autologous Treg cell therapy. In this review we will discuss key concepts related to the use of autologous Treg cell therapy for the treatment of T1D. Among these topics, we will discuss the notions of genetic control of Treg activity, Treg cellular plasticity, and requirements for antigen-specificity.

Keywords

Regulatory T cells Treg Type 1 diabetes Cellular therapy Immune regulation Transplantation Autoimmunity Genome wide association GWAS Cellular plasticity Interleukin-2 IL2RA Rapamycin Protein tyrosine phosphatase PTPN2 PTPN22 CTLA-4 

Notes

Acknowledgments

Funding for our prior studies cited in this review was provided by grants from the NIH (AI42288 and AI39250), a JDRF cord blood center grant to T.M.B. and Mark Atkinson, the JDRF Collaborative Center for Cell Therapy (CCCT) grant to Jeffrey Bluestone and T.M.B., and a JDRF Career Development Award to T.M.B. Additional project support was provided by the Brehm Coalition for Type 1 Diabetes.

The authors thank members of the Atkinson, Brusko, and Bluestone Laboratories, as well as the members of the JDRF CCCT for relevant discussions. While every effort was made to be inclusive, the authors apologize for any work that was inadvertently overlooked or not cited due to space constraints. No potential conflicts of interest relevant to this article were reported.

Disclosure

No potential conflicts of interest relevant to this article were reported.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • James A. Thompson
    • 1
  • Daniel Perry
    • 1
  • Todd M. Brusko
    • 1
    Email author
  1. 1.Department of Pathology, Immunology, and Laboratory Medicine, College of MedicineUniversity of FloridaGainesvilleUSA

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