title: Human treg cells are characterized by low/negative CD6 expression.
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 CD6(lo/-) 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 CD25hi FOXP3+ cells can be achieved in the combined CD6(lo/-) CD127(lo/-) population. We conclude that FOXP3+ nTreg cells are characterized by CD6(lo/-) 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.
authors.affiliation: Life Science Research, Beckman Coulter Inc., Miami, Florida, 33196.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Garcia Santana
authors.forename: James W
authors.initials: JW
authors.lastname: Tung
authors.forename: Sergei
authors.initials: S
authors.lastname: Gulnik
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D005434:Flow Cytometry / Q000379:methods*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: CD6; FOXP3; Treg; Treg-associated markers; human T cells; nTreg; natural regulatory T cells