title: Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4(+) T cell responses.
abstract: BACKGROUND
  A better understanding of allergen-specific CD4(+) T cell responses is needed to help improving immunological therapies. Objective To compare CD4(+) T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens.
  
  
  METHODS
  Major histocompatibility complex class II peptide tetramers were engineered to monitor allergen-specific T cell responses. After in vitro expansion, tetramer(+) cells were tested for surface markers using cytofluorometry. Cytokine gene expression and production were assessed using quantitative PCR and cytokine surface capture assays, respectively.
  
  
  RESULTS
  Tetramer(+) cells were detected in 19 patients allergic to house dust mites (HDM), seven allergic to birch pollen, 13 allergic to both and nine non-allergics with either an HLA-DRB1(*) 0101, (*) 0301, (*) 1501 or an HLA-DPB1(*) 0401 background. High-avidity T cells are elicited against the immunodominant Bet v 1(141-155) epitope, whereas broader low-avidity T cell responses are induced against Der p 1(16-30) ,(110-124) ,(171-185) and Der p 2(26-40,107-121) epitopes. Responses against Bet v 1 involve effector (CDL62 low, CCR7 low) or central (CD62L(+) , CCR7(+) ) memory cells in allergic and non-allergic individuals, respectively, whereas central memory cells are mostly detected against mite allergens. In non-allergics, both mite and Bet v 1-specific T cells produce IFN-γ and IL-10. In contrast to Bet v 1-driven Th2 responses, mite allergens induce highly polymorphic responses in allergics, including Th1, Th2/Th17 or mixed Th1/Th2 profiles. Mite-specific T cell frequencies in the blood remain in the range of 1-6 × 10(-4) CD4(+) T cells throughout the year.
  
  
  CONCLUSIONS
  Different memory CD4(+) T cell responses are elicited in the context of chronic vs. seasonal stimulation with the allergen(s). The heterogeneity in the patterns of CD4(+) T cell responses observed in patients allergic to HDMs should be taken into account for specific immunotherapy.
authors.affiliation: Stallergenes SA, Antony, France.
authors.forename: E
authors.initials: E
authors.lastname: Wambre
authors.forename: M
authors.initials: M
authors.lastname: Bonvalet
authors.forename: V B
authors.initials: VB
authors.lastname: Bodo
authors.forename: B
authors.initials: B
authors.lastname: Maillère
authors.forename: G
authors.initials: G
authors.lastname: Leclert
authors.forename: H
authors.initials: H
authors.lastname: Moussu
authors.forename: E
authors.initials: E
authors.lastname: Von Hofe
authors.forename: A
authors.initials: A
authors.lastname: Louise
authors.forename: A-M
authors.initials: AM
authors.lastname: Balazuc
authors.forename: D
authors.initials: D
authors.lastname: Ebo
authors.forename: C
authors.initials: C
authors.lastname: Hoarau
authors.forename: G
authors.initials: G
authors.lastname: Garcia
authors.forename: L
authors.initials: L
authors.lastname: Van Overtvelt
authors.forename: P
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D039741:Antigens, Dermatophagoides / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology*; D060829:Arthropod Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D012621:Seasons
chemical_list: D039741:Antigens, Dermatophagoides; D052179:Antigens, Plant; D060829:Arthropod Proteins; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; D000949:Histocompatibility Antigens Class II; C061312:Bet v 1 allergen, Betula; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1