Recommended Citation
Da Silva Antunes R, Frazier A, Pomés A, Calatroni A, Wood R, O'Connor G, Pongracic J, Hershey GK, Kercsmar C, Gill M, Liu A, Zoratti E, Kattan M, Busse P, Bacharier L, Teach S, Wheatley L, Togias A, Busse W, Jackson D, and Sette A. Down-Modulation of Cockroach (CR) Allergen-specific Th2 Cell Responses Following Subcutaneous German Cockroach Allergen Immunotherapy (SCIT). J Allergy Clin Immunol 2023; 151(2):AB322.
Document Type
Conference Proceeding
Publication Date
2-1-2023
Publication Title
J Allergy Clin Immunol
Abstract
Rationale: The responses of T cells to subcutaneous allergen immunotherapy (SCIT) are not fully elucidated. We conducted a functional immunological evaluation of cockroach (CR) allergen-specific CD4+ T cell reactivity in the double-blinded, placebo-controlled, multi-center CRITICAL study.
Methods: Participants (8-17 years of age) with mild to moderate, well-controlled asthma received 12 months of maintenance dosing of CR SCIT (n=20) or placebo (n=26). Peripheral blood mononuclear cells (PBMC) were isolated prior to, and after 12 months of therapy. CD4+ T cell responses at baseline and after treatment were assessed using overlapping peptide pools derived from 11 well-defined CR allergens and intracellular cytokine staining for IL-4, IFNg, and IL-10 production. T cell responses were further evaluated in terms of magnitude, cytokine polarization, and allergen immunodominance.
Results: Significant down-modulation of the total magnitude of CD4+ T cell responses was observed with SCIT but not placebo, with a significant change between groups (-4.46±0.82 vs. −1.81±0.72, respectively, p = 0.020). Responses were driven by a decrease in IL-4 (-4.87±0.86 vs. −1.09±0.75, p = 0.002) with unaltered IFNg and IL-10 production, reflecting a shift towards a Th1 polarization profile (1.35±0.58 vs. −0.37±0.50, in SCIT and placebo respectively, p = 0.031). The largest effects were observed against the allergens Bla g 5 and Bla g 9, which are dominantly recognized, suggesting that dominant responses are susceptible to modulation.
Conclusions: Our results demonstrate a significant down-regulation of CR-specific Th2 cell responses in urban children with asthma who received SCIT, compared with those who received placebo.
Volume
151
Issue
2
First Page
AB322