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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
Interferon-lambda-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells
Franck J D Mennechet1, Gilles Uzé
1Centre National de la Recherche Scientifique Unité mixte de recherche 5124, University of Montpellier, Place Eugéne Bataillon 34095, Montpellier cedex 5, France.
Blood
|February 16, 2006
Summary
Lambda interferons (IFN-lambdas) can generate tolerogenic dendritic cells (DCs) that suppress T-cell proliferation. This contrasts with type I interferons and may impact immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Lambda interferons (IFN-lambdas), also known as IL-28 and IL-29, are coexpressed with IFN-beta upon Toll-like receptor (TLR) stimulation in dendritic cells (DCs).
- IFN-lambdas share intracellular signaling pathways with type I interferons but utilize distinct membrane receptors.
- DC-derived interferons are crucial for DC differentiation and maturation.
Purpose of the Study:
- To investigate the specific effects of IFN-lambda on dendritic cell differentiation and function.
- To determine if IFN-lambdas can induce tolerogenic properties in DCs.
Main Methods:
- Monocyte-derived DCs were differentiated and treated with IFN-lambda.
- Expression of surface molecules (MHC class I, MHC class II, costimulatory molecules, CCR7) was analyzed.
- DC migration was assessed in SCID/Bg mice.
- Mixed lymphocyte reactions (MLR) were performed to evaluate T-cell responses.
Main Results:
- Differentiating DCs acquire IFN-lambda responsiveness via specific receptor expression.
- IFN-lambda-treated DCs showed high MHC class I and II, low costimulatory molecules, and expressed CCR7, enabling lymph node migration.
- IFN-lambda-treated DCs induced IL-2-dependent proliferation of a CD4(+)CD25(+)Foxp3(+) T-cell subset, suppressing proliferation induced by mature DCs.
Conclusions:
- IFN-lambdas can generate tolerogenic DCs with suppressive functions.
- This tolerogenic activity of IFN-lambdas may counteract the functions of IFN-beta.
- IFN-lambdas represent a distinct immunomodulatory pathway impacting DC function and T-cell responses.
