title: Depletion of CD4+CD25+CD127lo regulatory T cells does not increase allergen-driven T cell activation.
abstract: BACKGROUND
  It has been suggested that allergic diseases are caused by defective suppression of allergen-specific Th2 cells by CD4(+)CD25(+) regulatory T cells. However, such studies have been hampered by the difficulty in distinguishing regulatory T cells from CD25-expressing activated T cells. Recently, it was shown that conventional T cells expressed high levels of CD127, whereas regulatory T cells were CD127(lo), allowing discrimination between these distinct T cell subpopulations.
  
  
  OBJECTIVE
  The aim of this study was to study whether the putative regulatory subset defined as CD4(+)CD25(+)CD127(lo) was involved in grass pollen-reactive T cell responses.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) were obtained from allergic donors and non-atopic controls out of season. Grass pollen-induced cytokine production and proliferation were compared in cultures of undepleted cells and cells depleted of CD4(+)CD25(+), CD4(+)CD25(+)CD127(hi) or CD4(+)CD25(+)CD127(lo) T cells.
  
  
  RESULTS
  Undepleted cell cultures from allergic patients showed significantly increased proliferation and Th2 cytokine production compared with non-atopic controls. Depletion of all CD25(+) T cells did not increase cytokine production or proliferation, and more importantly, no increase in Th2 cytokine production or proliferation was observed in cell cultures depleted of CD4(+)CD25(+)CD127(lo) cells (putative regulatory T cells) compared with undepleted PBMCs in both the allergic and the non-atopic group.
  
  
  CONCLUSIONS
  Our study showed that T cells from grass pollen-allergic patients and non-atopic controls responded very differently to grass pollen extract, but this difference could not be explained by differences in regulatory T cell function. Further studies are needed to understand the importance of regulatory T cells in allergy.
authors.affiliation: Laboratory for Immunohistochemistry and Immunopathology, Centre for Immune Regulation, Institute of Pathology, University of Oslo, Oslo, Norway. ingebjorg.skrindo@rr-research.no
authors.forename: I
authors.initials: I
authors.lastname: Skrindo
authors.forename: L
authors.initials: L
authors.lastname: Farkas
authors.forename: E O
authors.initials: EO
authors.lastname: Kvale
authors.forename: F-E
authors.initials: FE
authors.lastname: Johansen
authors.forename: F L
authors.initials: FL
authors.lastname: Jahnsen
mesh_terms: D000328:Adult; D052179:Antigens, Plant / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015848:Interleukin-5 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D031784:Phleum / Q000276:immunology; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D052179:Antigens, Plant; D018793:Interleukin-13; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; D053699:Interleukin-7 Receptor alpha Subunit; D007371:Interferon-gamma