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Alteration of Regulatory T Cells in Type 1 Diabetes Mellitus: A Comprehensive Review

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Abstract

Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells. Numerous studies have demonstrated the key role of CD4+CD25+FoxP3+ regulatory T cells (Tregs) in the development of T1DM. However, the changes in Treg expression and function as well as the regulation of these activities are not clearly elucidated. Most studies on the role of Tregs in T1DM were performed on peripheral blood rather than pancreas or pancreatic lymph nodes. Tissue-based studies are more difficult to perform, and there is a lack of histological data to support the role of Tregs in T1DM. In spite of this, strategies to increase Treg cell number and/or function have been viewed as potential therapeutic approaches in treating T1DM, and several clinical trials using these strategies have already emerged. Notably, many trials fail to demonstrate clinical response even when Treg treatment successfully boosts Tregs. In view of this, whether a failure of Tregs does exist and contribute to the development of T1DM and whether more Tregs would be clinically beneficial to patients should be carefully taken into consideration before applying Tregs as treatments in T1DM.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No.81170725, 81070672), Program for Changjiang Scholars and Innovative Research Team in University (IRT1195), the National key technology R&D program (2012BAI02B04), Research Fund for the Doctoral Program of Higher Education of China 20120162110044; Yufei Xiang is supposed by a European Foundation for the Study of Diabetes-China Diabetes Society (EFSD-CDS) fellowship (2013).

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All authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Diabetes Center, The Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Central South University, 139 Renmin Zhong Road, Changsha, Hunan, 410011, People’s Republic of China

    Tingting Tan, Yufei Xiang & Zhiguang Zhou

  2. Division of Allergy and Immunology, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University, 1600 Rockland Road, Wilmington, DE, 19803, USA

    Christopher Chang

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  1. Tingting Tan
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  2. Yufei Xiang
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  3. Christopher Chang
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Correspondence to Zhiguang Zhou.

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Tan, T., Xiang, Y., Chang, C. et al. Alteration of Regulatory T Cells in Type 1 Diabetes Mellitus: A Comprehensive Review. Clinic Rev Allerg Immunol 47, 234–243 (2014). https://doi.org/10.1007/s12016-014-8440-0

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