Article

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: 9.78). 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.

0 Bookmarks
 · 
110 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Natural regulatory T cells (nTreg) can suppress different immune-cell responses and maintain the balance between tolerance and immunity in the individual. These cells are defined by CD4+, CD25hi, and FOXP3+ expression, although a variety of other nTreg-associated markers have been reported to be expressed at different levels (e.g., HLA-DR, CTLA-4, GARP, Helios, CD39, etc.), presumably reflecting different functional stages of the heterogeneous nTreg population. Several markers show low/negative expression (i.e., CD127, CD49d, and CD26), but none of these markers are specific to nTreg. CD25hi expression has been a useful surface marker to identify/isolate nTreg; however, CD25 is also expressed on “adaptive” or “induced” Treg, as well as in activated conventional T cells. In addition, the fact that FOXP3 is also found in CD25 low/negative CD4+ T cells, and in a subset of CD8+ T cells, further complicates the definition of a specific nTreg marker. Although CD4+, CD25hi, and CD127low/negative markers characterize the majority of nTreg, it is still imperative to find additional surface-marker combinations that improve the identification/isolation of nTreg and their subsets. Herein, we present evidence that CD4+CD25hi CD6lo/− nTreg have high expression of FOXP3and exhibit in vitro suppressive activity on CD8+ T-cell proliferation. Dot-plot analyses of CD4+ cells, with CD6, CD127, CD49d, or CD26 reveal that a higher enrichment yield of CD25hiFOXP3+ cells can be achieved in the combined CD6lo/−CD127lo/− population. We conclude that FOXP3+ nTreg cells are characterized by CD6lo/− expression, providing a new tool for the identification of nTreg cells without recourse to intracellular staining, and for the purification of these cells by negative selection. © 2014 International Society for Advancement of Cytometry
    Cytometry Part A 08/2014; · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CD147 is a widely expressed integral plasma membrane glycoprotein and has been involved in a variety of physiological and pathological activities in combination with different partners, including cyclophilins, caveolin-1, monocarboxylate transporters, and integrins. Recent data demonstrate that both CyPA and CD147 significantly contribute to renal inflammation, acute kidney injury, renal fibrosis, and renal cell carcinoma. Here we review the current understanding of cyclophilin A and CD147 expression and functions in kidney diseases and potential implications for treatment of kidney diseases.
    Mediators of Inflammation 01/2014; 2014:728673. · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Suppressor cells regulate immune responses during chronic viral infection by limiting immunopathology associated with inflammation and immune activation. This dampening of adaptive immune responses can be harmful in HIV-1 infection as it also prevents the immune system from clearing the virus, leading to viral persistence and prolonged antigen expression that often leads to immune exhaustion. A current priority is to find the best strategy to target and manipulate key molecules such as CD39 that suppress anti-HIV-1 immune responses.
    Current Opinion in HIV and AIDS 07/2014; · 4.39 Impact Factor