Immune Netw.  2016 Oct;16(5):281-285. 10.4110/in.2016.16.5.281.

Development of Auto Antigen-specific Regulatory T Cells for Diabetes Immunotherapy

• Song J

• KMID: 2355021
• DOI: http://doi.org/10.4110/in.2016.16.5.281

Abstract

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet β cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

Keyword

Stem cells; Regulatory T cells; Immunotherapy; Tolerance; T cells; Diabetes

MeSH Terms

Adoptive Transfer
Autoimmune Diseases
Autoimmunity
Glucose
Homeostasis
Immunosuppression
Immunotherapy*
Peripheral Tolerance
Pluripotent Stem Cells
Stem Cells
T-Lymphocytes
T-Lymphocytes, Regulatory*
Glucose

Figure

• 

  Figure 1 Populations of auto Ag-specific Tregs that can be generated for cell-based therapies in T1D. Auto Ag specific Tregs can be generated by TCR transduction of CD4+ Tregs, TCR/FoxP3-gene transduction of CD4+ T cells, or TCR/FoxP3-gene transduction of PSCs, followed T-cell differentiation driven by Notch ligands.

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