title: Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy.
abstract: BACKGROUND
  Different populations of T cells are involved in the pathogenesis of allergic diseases.
  
  
  OBJECTIVE
  We investigated changes in TH-cell populations in patients with allergies after specific immunotherapy (SIT).
  
  
  METHODS
  PBMCs were isolated from patients with allergies who received SIT and those who did not (controls). We tested the ability of peptides from 93 timothy grass (TG) proteins to induce T-cell responses (cytokine production). We used ELISPOT and staining assays for intracellular cytokines to measure the production of IL-4, IL-5, IL-13, IFN-γ, and IL-10.
  
  
  RESULTS
  Compared with PBMCs from controls, PBMCs from patients who received SIT produced lower levels of TH2 cytokines on incubation with several different TG peptides. These data were used to select 20 peptides to be tested in an independent cohort of 20 patients with allergies who received SIT and 20 controls. We again observed a significant decrease in the production of TH2 cytokines, and an increase in the production of the TH1 cytokine IFN-γ, in PBMCs from the validation groups. These changes correlated with improved symptoms after SIT. Immunization with this selected pool of peptides (or their associated antigens) could protect a substantial proportion of the population from TG allergy.
  
  
  CONCLUSIONS
  We observed a significant decrease in the production of TH2 cytokines by PBMCs from patients who received SIT for TG allergy compared to those who did not. These changes might be used to monitor response to therapy. The decrease occurred in response to antigens that elicit little (if any) IgE responses; these antigens might be developed for use in immunotherapy.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
authors.forename: Véronique
authors.initials: V
authors.lastname: Schulten
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
authors.forename: Victoria
authors.initials: V
authors.lastname: Tripple
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
authors.forename: Jason
authors.initials: J
authors.lastname: Greenbaum
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
authors.forename: April
authors.initials: A
authors.lastname: Frazier
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colo.
authors.forename: Rafeul
authors.initials: R
authors.lastname: Alam
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, Calif.
authors.forename: David
authors.initials: D
authors.lastname: Broide
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif. Electronic address: alex@liai.org.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D052179:Antigens, Plant / Q000008:administration & dosage* / Q000737:chemistry; D016207:Cytokines / Q000276:immunology; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D031784:Phleum / Q000737:chemistry*; D010940:Plant Proteins / Q000008:administration & dosage* / Q000737:chemistry; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D052179:Antigens, Plant; D016207:Cytokines; D010455:Peptides; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: T cells; cytokine; specific immunotherapy; timothy grass