title: Allergen-specific T cells from birch-pollen-allergic patients and healthy controls differ in T helper 2 cytokine and in interleukin-10 production.
abstract: BACKGROUND
  T helper (Th)2 cells play an important role in the development of IgE-mediated diseases, with local overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic inflammation. Furthermore, IL-10 has been suggested to play a modulatory role in the induction and maintenance of allergen-specific tolerance in human atopic diseases.
  
  
  OBJECTIVE
  We studied whether circulating allergen-specific Th2 cells persist outside the season of exposure in patients mono-sensitized to birch pollen and whether healthy control individuals also have allergen-specific Th2 cells. We also studied whether IL-10-producing allergen-specific T cells can be found in circulation either in healthy controls or in allergic patients.
  
  
  METHODS
  Blood was drawn outside the birch-pollen season from 15 birch-pollen-allergic patients, with seasonal respiratory symptoms and with (n=12) or without (n=3) oral allergy syndrome, and from 10 matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with recombinant Bet v 1 allergen, control antigen tetanus toxoid (TT) and anti-CD3/CD80. In part of the cultures, rIL-4 was added in order to reinforce the allergen-specific Th2 cell responses.
  
  
  RESULTS
  In the presence of rBet v 1, T cells from allergic patients, but not from healthy controls, produced IL-4, IL-5 and IL-13. IL-5 production by patients' T cells was further enhanced by adding more IL-4. In contrast, rBet v 1 together with IL-4-induced significant IL-10 production in control subjects but not in patients. Both Th1 and Th2 cytokines were equally induced by polyclonal stimulation in allergic patients and controls, but in the presence of IL-4, polyclonally induced IL-10 production was lower in the patient group.
  
  
  CONCLUSIONS
  rBet v 1-specific Th2 cells circulate outside the season of exposure in the blood of birch-pollen-allergic subjects but not in healthy controls. Allergen-specific T cells were also demonstrated in controls but these cells produce IL-10 when stimulated with rBet v 1 in the presence of IL-4. Our data reveal a different allergen-induced cytokine profile in birch-pollen-allergic patients vs. controls, and suggest that a regulatory mechanism involving IL-4-induced allergen-specific IL-10 production might be defective in allergic subjects.
authors.affiliation: Division of Clinical Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium.
authors.forename: D M A
authors.initials: DM
authors.lastname: Bullens
authors.forename: C
authors.initials: C
authors.lastname: Van Den Keybus
authors.forename: E
authors.initials: E
authors.lastname: Dilissen
authors.forename: A
authors.initials: A
authors.lastname: Kasran
authors.forename: J L
authors.initials: JL
authors.lastname: Ceuppens
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D010940:Plant Proteins / Q000276:immunology*; D018709:Statistics, Nonparametric; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D016753:Interleukin-10; D015847:Interleukin-4