Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy

Background: Different populations of T cells are involved in the pathogenesis of allergic diseases. Objective: We investigated changes in T-H-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-gamma, and IL-10. Results: Compared with PBMCs from controls, PBMCs from patients who received SIT produced lower levels of T(H)2 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 T(H)2 cytokines, and an increase in the production of the T(H)1 cytokine IFN-g, 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 T(H)2 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.