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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
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Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells
Anne-Sophie Gautron1, Margarita Dominguez-Villar1, Marine de Marcken1
1Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520.
European Journal of Immunology
|May 20, 2014
Summary
T-cell immunoglobulin and mucin domain 3 (TIM-3) on regulatory T cells (Tregs) is upregulated upon activation. TIM-3 expressing Tregs effectively suppress pathogenic Th1 and Th17 cell responses, highlighting its role in immune tolerance.
Area of Science:
- Immunology
- Cell Biology
Background:
- T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune checkpoint molecule.
- TIM-3 regulates T-cell responses and immune tolerance.
- In mice, TIM-3 is expressed on regulatory T cells (Tregs) and modulates alloimmunity.
Purpose of the Study:
- To investigate TIM-3 expression on human Tregs.
- To determine the role of TIM-3 in human Treg-mediated T-cell suppression.
Main Methods:
- Flow cytometry to assess TIM-3 expression on human Tregs.
- Analysis of gene expression (LAG3, CTLA4, FOXP3, STAT-3, IL10, etc.) in TIM-3(+) and TIM-3(-) Tregs.
- T-cell suppression assays evaluating Th1 and Th17 cell responses.
Main Results:
- TIM-3 is not constitutively expressed on human Tregs ex vivo but is upregulated after activation.
- TIM-3(+) human Tregs exhibit enhanced expression of suppressive markers (LAG3, CTLA4, FOXP3).
- TIM-3(+) Tregs demonstrate superior suppression of Th1 and Th17 effector cells compared to TIM-3(-) Tregs, which show impaired suppression of Th17 cells.
Conclusions:
- TIM-3 expression on activated human Tregs identifies a potent suppressive subset.
- TIM-3(+) Tregs are crucial for inhibiting pathogenic Th1 and Th17 cell responses.
- TIM-3 plays a significant role in regulating immune tolerance via human Tregs.
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