title: Characterisation of CD154+ T cells following ex vivo birch allergen stimulation defines a close relationship between T cell subsets in healthy volunteers.
abstract: BACKGROUND
  Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We hypothesised that the relationship between these T cell subsets could be better defined using a short-term allergen stimulation system followed by direct analysis of CD154-positive T cells. Using peripheral blood samples from birch pollinosis patients and healthy non-atopic controls, we sought to explore the frequencies and phenotype of birch-stimulated CD154-positive T helper cells following ex vivo birch allergen stimulation.
  
  
  RESULTS
  Activated CD154-positive Th1, Th2 and Tr1-like cells, that co-expressed IFNγ, IL-4 and IL-10 respectively, were identified in both birch-allergic and non-allergic participants. We observed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. The relationship between Th1, Th2 and Tr1-like responses was dysregulated in birch-allergic patients, with abrogation of the IL-10 response and a higher Th2: Th1 ratio. A close correlation was observed between Th2 cell frequency and the absolute concentration of birch-specific IgE within the birch-allergic group, and we confirmed previous reports of a more differentiated T cell phenotype in allergic subjects.
  
  
  CONCLUSIONS
  The findings demonstrate an important balance between IFNγ, IL-4 and IL-10 T cell responses to birch allergen in health, where Th2 responses to allergens were frequently observed, but apparently balanced by Th1 and regulatory responses. The detection of CD154 positive T cells after short-term antigen stimulation may be a useful method for the detection of T cell responses to allergens when cost, speed and convenience are priorities.
authors.affiliation: Brighton and Sussex Medical School, Division of Clinical Medicine, Pathogen-Host-Interactions Group, University of Sussex, Brighton, BN1 9PS, UK.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Smith
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Gray
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cheek
authors.forename: Femi
authors.initials: F
authors.lastname: Saleh
authors.forename: Jo
authors.initials: J
authors.lastname: Lavender
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Frew
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tarzi
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes; D005260:Female; D006262:Health; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010641:Phenotype; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D012621:Seasons; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D000939:Epitopes; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand; D017493:Leukocyte Common Antigens