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Updated: May 29, 2026
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
CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells
Therese Solstad1, Simer Jit Bains, Johannes Landskron
1Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Oslo, Norway.
Insights
CD147 is identified as a marker for activated human regulatory T cells (Tregs). This finding helps distinguish between resting and activated Tregs, offering insights into immune homeostasis and potential therapeutic manipulation.
Area of Science:
- Immunology
- Cell Biology
- Proteomics
Background:
- Human CD4(+)FoxP3(+) T cells exhibit significant functional and phenotypic heterogeneity.
- Understanding the dynamics within this subset is crucial for immune regulation.
Purpose of the Study:
- To identify protein markers distinguishing functional subsets within human CD4(+)FoxP3(+) T cells.
- To investigate the role of CD147 in regulatory T cell (Treg) activation and function.
Main Methods:
- Subcellular fractionation and proteomics to analyze protein expression differences between CD4(+)CD25(+) and CD4(+)CD25(-) T cells.
- Cell surface protein analysis, including CD147, CD25, FoxP3, and CTLA-4.
- Phenotypical and functional analyses of sorted Treg subsets.
- Cytokine production assays.
Main Results:
- Proteomic analysis identified cell surface proteins including CD71, CD95, CD147, and CD148 on human Tregs.
- CD147 expression correlated with CD25, FoxP3, and CTLA-4.
- CD147 distinguishes between resting (CD45RA(+)) and activated (CD45RO(+)) FoxP3(+) T cells.
- CD147(+) Tregs represent an activated, highly suppressive subset with distinct cytokine production profiles.
Conclusions:
- CD147 serves as a direct marker for activated regulatory T cells (Tregs) within the CD4(+)FoxP3(+) population.
- CD147 can differentiate Tregs based on activation status and suppressive capacity.
- This marker may offer novel strategies for manipulating immune homeostasis.
Abstract:
Human CD4(+)FoxP3(+) T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(-) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells (Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-α, IFN-γ, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis.
