title: Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects.
abstract: OBJECTIVE
  The trace element zinc is essential for immune function and its regulation. Since zinc deficiency and allergic hyperresponsive reactions are often accompanied, the influence of zinc on allergen-induced cell growth, CD4+ regulatory T (Treg) cell numbers and cytokine expression during allergic immune reactions was investigated.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) from non-atopic and atopic subjects were treated with timothy grass allergen pre-incubated with or without zinc. Proliferation was determined by analyzing the incorporation of3H-thymidine. Intracellular zinc and Foxp3 levels and cell surface antigens were measured by FACS, cytokine expression by ELISA and real-time PCR.
  
  
  RESULTS
  Incubation with 50 μM zinc sulfate (Zn50) enhances cytosolic zinc concentrations in CD3+ T cells. The data also reveal that the combination of Zn50 plus allergen significantly reduces PBMC proliferation of atopic subjects. Additionally, Zn50 plus allergen enhances Th1 cytokine responses shown by increased interferon (IFN)-γ/interleukin (IL)-10 ratios as well as enhanced tumor necrosis factor-α release. In response to allergen, zinc increases Treg cells and upregulates the mRNA expression of cytotoxic T-lymphocyte antigen-4 in atopic subjects. Interestingly, Zn50 alone leads to an increase of CD4+CD25high(hi)+ cells in atopic and non-atopic subjects.
  
  
  CONCLUSIONS
  Zinc may regulate unwanted hyperresponsive immune reactions by suppressing proliferation through a significant shift from IL-10 to the Th1 cytokine IFN-γ, and enhanced regulatory T cell numbers. Therefore, zinc supplementation may be a promising tool for the therapy of allergies, without negatively affecting the immune system.
authors.affiliation: Institute of Immunology, Faculty of Medicine, University Hospital, RWTH Aachen University, Pauwelstr. 30, 52074, Aachen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rosenkranz
authors.affiliation: Institute of Medical Statistics, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hilgers
authors.affiliation: Institute of Immunology, Faculty of Medicine, University Hospital, RWTH Aachen University, Pauwelstr. 30, 52074, Aachen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Uciechowski
authors.affiliation: Division of Clinical and Molecular Allergology, Research Center Borstel, Airway Research Center North (ARCN), Borstel, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Petersen
authors.affiliation: Institute of Immunology, Faculty of Medicine, University Hospital, RWTH Aachen University, Pauwelstr. 30, 52074, Aachen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Plümäkers
authors.affiliation: Institute of Immunology, Faculty of Medicine, University Hospital, RWTH Aachen University, Pauwelstr. 30, 52074, Aachen, Germany. LRink@UKAachen.de.
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
mesh_terms: D000485:Allergens / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D031784:Phleum / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000485:Allergens; C508609:IL10 protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D015032:Zinc
keywords: Allergy; Foxp3; Nutritional immunology; Regulatory T cells; Treg; Zinc