title: CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells.
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.
authors.affiliation: Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Oslo, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Solstad
authors.forename: Simer Jit
authors.initials: SJ
authors.lastname: Bains
authors.forename: Johannes
authors.initials: J
authors.lastname: Landskron
authors.forename: Einar Martin
authors.initials: EM
authors.lastname: Aandahl
authors.forename: Bernd
authors.initials: B
authors.lastname: Thiede
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
authors.forename: Knut Martin
authors.initials: KM
authors.lastname: Torgersen
mesh_terms: D051926:Basigin / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D040901:Proteomics; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000378:metabolism
chemical_list: C497886:BSG protein, human; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051926:Basigin; D017493:Leukocyte Common Antigens