title: Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals.
abstract: BACKGROUND
  Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We sought to utilise our short-term CD154 detection method to further analyse the relationship between these T cell subsets and investigate differences between seasonal and perennial allergens. Using peripheral blood samples from grass-allergic, cat-allergic and healthy non-atopic subjects, we compared the frequencies and phenotype of CD154-positive T helper cells following stimulation with seasonal (grass) and perennial (cat dander) allergens.
  
  
  RESULTS
  We identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. Activated Th1, Th2 and Tr1-like cells, that co-express IFNγ, IL4 and IL10, respectively, were identified in varying proportions in grass-allergic, cat-allergic and non-allergic individuals. We confirmed 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. This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We confirmed previous reports of a late-differentiated T cell phenotype in response to seasonal allergens compared to early-differentiated T cell responses to perennial allergens.
  
  
  CONCLUSIONS
  The findings confirm our existing work illustrating an important balance between Th1, Th2 and Tr1-like responses to allergens in health, where Th2 responses are frequently observed, but balanced by Th1 and regulatory responses. We confirm previous tetramer-based reports of phenotypic differences in T cells responding to seasonal and perennial allergens.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Smith
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Gray
authors.forename: Femi
authors.initials: F
authors.lastname: Saleh
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cheek
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Frew
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
authors.affiliation: Brighton and Sussex Medical School, division of clinical medicine, pathogen-host-interactions group, University of Sussex, Brighton BN1 9PS, UK. M.Tarzi@bsms.ac.uk.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tarzi
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D023201:CD40 Ligand / Q000276:immunology* / Q000378:metabolism; D002415:Cats; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D000485:Allergens; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma