title: Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.
abstract: BACKGROUND
  The main obstacle to elucidating the role of CD4(+) T cells in allergen-specific immunotherapy (SIT) has been the absence of an adequately sensitive approach to directly characterize rare allergen-specific T cells without introducing substantial phenotypic modifications by means of in vitro amplification.
  
  
  OBJECTIVE
  We sought to monitor, in physiological conditions, the allergen-specific CD4(+) T cells generated during natural pollen exposure and during allergy vaccination.
  
  
  METHODS
  Alder pollen allergy was used as a model for studying seasonal allergies. Allergen-specific CD4(+) T cells were tracked and characterized in 12 subjects with alder pollen allergy, 6 nonallergic subjects, and 9 allergy vaccine-treated subjects by using peptide-MHC class II tetramers.
  
  
  RESULTS
  Allergen-specific CD4(+) T cells were detected in all of the subjects with alder pollen allergy and nonallergic subjects tested. Pathogenic responses--chemoattractant receptor homologous molecule expressed on T(H)2 lymphocytes (CRTH2) expression and T(H)2 cytokine production--are specifically associated with terminally differentiated (CD27(-)) allergen-specific CD4(+) T cells, which dominate in allergic subjects but are absent in nonallergic subjects. In contrast, CD27(+) allergen-specific CD4(+) T cells are present at low frequencies in both allergic and nonallergic subjects and reflect classical features of the protective immune response with high expression of IL-10 and IFN-γ. Restoration of a protective response during SIT appears to be due to the preferential deletion of pathogenic (CD27(-)) allergen-specific CD4(+) T cells accompanied by IL-10 induction in surviving CD27(+) allergen-specific CD4(+) T cells.
  
  
  CONCLUSIONS
  Differentiation stage divides allergen-specific CD4(+) T cells into 2 distinct subpopulations with unique functional properties and different fates during SIT.
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Wash 98101, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Wambre
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: DeLong
authors.forename: Eddie A
authors.initials: EA
authors.lastname: James
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: LaFond
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D003888:Desensitization, Immunologic; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008875:Middle Aged; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D012882:Skin Tests
chemical_list: D000485:Allergens; C067879:Aln g I protein, Alnus glutinosa; D052179:Antigens, Plant; D016207:Cytokines; D010940:Plant Proteins; D007073:Immunoglobulin E