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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
IL-2Rbeta links IL-2R signaling with Foxp3 expression
David M Soper1, Deborah J Kasprowicz, Steven F Ziegler
1Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.
European Journal of Immunology
|June 15, 2007
Summary
Interleukin-2 receptor beta (IL-2Rbeta) signaling is crucial for regulatory T cell (Treg) development and function. Mice lacking IL-2Rbeta show reduced Treg numbers and develop fatal autoimmune disease.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Immunological tolerance prevents autoimmune diseases.
- Forkhead box protein 3 (Foxp3) is essential for regulatory T cell (Treg) differentiation and function.
- Interleukin-2 (IL-2) signaling is implicated in Treg development and maintenance.
Purpose of the Study:
- To directly investigate the impact of IL-2 signaling on Treg development and function.
- To analyze the role of IL-2 receptor (IL-2R) components in vivo.
Main Methods:
- Analysis of mice genetically deficient in IL-2Ralpha (CD25) and IL-2Rbeta (CD122).
- Assessment of Treg populations in the thymus and periphery.
- Evaluation of lymphoproliferative disease onset.
- Investigation of Foxp3 transgene expression effects.
Main Results:
- Mice lacking CD25 showed a minor decrease in thymic Treg but unchanged peripheral Treg numbers.
- Mice deficient in CD122 exhibited a significant reduction in both thymic and peripheral Treg.
- CD122-deficient mice rapidly developed fatal lymphoproliferative disease.
- Expression of a Foxp3 transgene rescued Treg populations and prevented autoimmunity in CD122-deficient mice.
Conclusions:
- IL-2 signaling via IL-2Rbeta is indispensable for the development and homeostasis of Foxp3(+) Treg cells.
- Disruption of IL-2Rbeta signaling leads to Treg deficiency and severe autoimmunity.
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