title: Cord blood derived CD4+ CD25(high) T cells become functional regulatory T cells upon antigen encounter.
abstract: BACKGROUND
  Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these "excessive" responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself.
  
  
  METHODS
  Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([(3)H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4(+)CD25(high)FoxP3(+) T cells were characterized by mRNA analysis and flow cytometry.
  
  
  RESULTS
  Cord blood derived CD4(+)CD25(high) cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4(+)CD25(high) cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3(+)CD4(+)CD25(high)cells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4(+)CD25(+)CD127(low)) is highly suppressive even without prior antigen exposure.
  
  
  CONCLUSIONS
  Cord blood harbors a very small subset of CD4(+)CD25(high) Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mayer
authors.forename: Christina
authors.initials: C
authors.lastname: Bannert
authors.forename: Saskia
authors.initials: S
authors.lastname: Gruber
authors.forename: Sven
authors.initials: S
authors.lastname: Klunker
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szépfalusi
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiwegger
mesh_terms: D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D007782:Lactoglobulins / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; C087215:LRRC32 protein, human; D007782:Lactoglobulins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta