Véronique Schulten1, Victoria Tripple1, John Sidney1, Jason Greenbaum1, April Frazier1, Rafeul Alam2, David Broide3, Bjoern Peters1, Alessandro Sette4. 1. Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif. 2. Department of Medicine, National Jewish Health, Denver, Colo. 3. Department of Medicine, University of California, San Diego, La Jolla, Calif. 4. Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, Calif. Electronic address: alex@liai.org.
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.
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 TGpeptides. 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: Denise M McKinney; Scott Southwood; Denise Hinz; Carla Oseroff; Cecilia S Lindestam Arlehamn; Veronique Schulten; Randy Taplitz; David Broide; Willem A Hanekom; Thomas J Scriba; Robert Wood; Rafeul Alam; Bjoern Peters; John Sidney; Alessandro Sette Journal: Immunogenetics Date: 2013-02-08 Impact factor: 2.846
Authors: S Vrtala; M Susani; W R Sperr; P Valent; S Laffer; C Dolecek; D Kraft; R Valenta Journal: J Allergy Clin Immunol Date: 1996-03 Impact factor: 10.793
Authors: Mübeccel Akdis; Johan Verhagen; Alison Taylor; Fariba Karamloo; Christian Karagiannidis; Reto Crameri; Sarah Thunberg; Günnur Deniz; Rudolf Valenta; Helmut Fiebig; Christian Kegel; Rainer Disch; Carsten B Schmidt-Weber; Kurt Blaser; Cezmi A Akdis Journal: J Exp Med Date: 2004-06-01 Impact factor: 14.307
Authors: J Pham; C Oseroff; D Hinz; J Sidney; S Paul; J Greenbaum; R Vita; E Phillips; S Mallal; B Peters; A Sette Journal: Clin Exp Allergy Date: 2016-07-26 Impact factor: 5.018
Authors: Sinu Paul; Myles B C Dillon; Cecilia S Lindestam Arlehamn; Huang Huang; Mark M Davis; Denise M McKinney; Thomas Jens Scriba; John Sidney; Bjoern Peters; Alessandro Sette Journal: J Immunol Date: 2015-05-06 Impact factor: 5.422
Authors: Carla Oseroff; John Pham; April Frazier; Denise Hinz; John Sidney; Sinu Paul; Jason A Greenbaum; Randi Vita; Bjoern Peters; Véronique Schulten; Alessandro Sette Journal: Ann Allergy Asthma Immunol Date: 2016-12 Impact factor: 6.347
Authors: V Schulten; V Tripple; K Aasbjerg; V Backer; G Lund; P A Würtzen; A Sette; B Peters Journal: Clin Exp Allergy Date: 2016-03 Impact factor: 5.018
Authors: M B C Dillon; V Schulten; C Oseroff; S Paul; L M Dullanty; A Frazier; X Belles; M D Piulachs; C Visness; L Bacharier; G R Bloomberg; P Busse; J Sidney; B Peters; A Sette Journal: Clin Exp Allergy Date: 2015-12 Impact factor: 5.018