CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells

Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Oslo, Norway.
Blood (Impact Factor: 10.43). 09/2011; 118(19):5141-51. DOI: 10.1182/blood-2011-02-339242
Source: PubMed

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.

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    • "A detailed knowledge of human FOXP3 + cell subsets is essential for a better understanding of the regulation of human FOXP3 expression, the study of abnormalities among the FOXP3 + subpopulations in autoimmune diseases and allergies, and the selection and purification of the most promising subpopulation(s) of Treg cells for in vitro expansion and adoptive transfer (Fujii et al., 2011; Miyara and Sakaguchi, 2011). Recent studies from different groups have demonstrated the heterogeneity of human FOXP3 + cells and have begun to define and characterize possible subsets (Baecher-Allan et al., 2001; Ito et al., 2008; Thornton et al., 2010; Akimova et al., 2011; Bianchini et al., 2011; Schuler et al., 2011; Solstad et al., 2011; Duhen et al., 2012). "
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