title: ZAP70 expression in regulatory T cells in allergic rhinitis: effect of immunotherapy.
abstract: BACKGROUND
  Some allergic diseases may be accompanied by inappropriate number or malfunction of regulatory T cells, which seems to be modified by specific immunotherapy (SIT).
  
  
  OBJECTIVE
  To assess if immunotherapy affects regulatory T lymphocytes (Tregs) and their expression of zeta chain associated protein kinase (Zap70), which is essential for T cell activation and intracellular signal downstream transduction.
  
  
  METHODS
  A 3-year prospective, placebo-controlled, double-blind trial of grass SIT was conducted. Forty-one patients sensitized to grass pollen with intermittent allergic rhinitis were randomized to receive SIT (n = 21) or placebo (n = 20) and 15 healthy were included as a control. Concentration of exhaled nitric oxide (ENO), lung function, symptom scores, the subsets of regulatory T cells (CD4(+)  CD25hiCD127low) which express ZAP70 and the level of ZAP70 expression in this subset were assessed at baseline and during the treatment period: before the onset, at the height of the pollen season and after the end of the pollen season.
  
  
  RESULTS
  The concentration of nitric oxide and the symptom score were significantly higher in allergic rhinitis patients as compared with the control group. Natural allergen stimulation diminished both the numbers of regulatory T cells that express ZAP70 and the expression of Zap70 within these cells. In the second year of treatment, immunotherapy reduced significantly the symptom scores, concentrations of ENO (P < 0.01), intensively increased expression of ZAP70 in regulatory T cells (P < 0.001) and the percentage of cells that express ZAP70 (P < 0.05) at the height of the pollen season. Placebo treatment did not reduce scores, ENO (P > 0.05) nor had influence on Zap70 expression (P > 0.05).
  
  
  CONCLUSIONS
  SIT with grass pollen effectively reduces rhinitis severity and affects allergic airway inflammation reflected by reduction of ENO. Beneficial role of immunotherapy may result not only from the induction of Treg numbers but especially from cell activation and restitution of Treg intracellular signal transduction.
authors.affiliation: Department of Pneumonology and Allergy, Medical University of Lodz, 90-153 Lodz, Poland. maciej_ciebiada@op.pl
authors.forename: M
authors.initials: M
authors.lastname: Ciebiada
authors.forename: K
authors.initials: K
authors.lastname: Kasztalska
authors.forename: M
authors.initials: M
authors.lastname: Gorska-Ciebiada
authors.forename: P
authors.initials: P
authors.lastname: Górski
mesh_terms: D000328:Adult; D052179:Antigens, Plant / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008297:Male; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage; D011446:Prospective Studies; D012129:Respiratory Function Tests; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D052179:Antigens, Plant; D010936:Plant Extracts; C451253:grass pollen extract, alum-adsorbed; D009569:Nitric Oxide; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human