Cockroach immunotherapy modulates dominant T-cell responses independent of allergen extract content.

Abstract

T-cell responses to the individual components of allergen extracts have not been fully elucidated in subcutaneous allergen immunotherapy (SCIT). Specifically, it is unknown whether T-cell responses to immunodominant allergens are more or less sensitive to modulation, and whether allergen abundance in the immunotherapy extract influences T-cell response modulation. To fill these gaps, we evaluated CD4⁺ T-cell reactivity specific to each of the main cockroach allergens in the double-blinded, placebo controlled, multicenter CRITICAL (NCT03541187) SCIT trial. Participants aged 8-17 years with mild-to-moderate, well-controlled asthma received 12 months' dosing with cockroach SCIT (n = 20) or placebo (n = 26). Peripheral blood mononuclear cells were isolated before 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 cockroach allergens and intracellular cytokine staining for IL-4, IFN-γ, and IL-10 production. T-cell responses were evaluated for magnitude, cytokine polarization, allergen immunodominance, and correlation with allergen content in the cockroach SCIT extract. SCIT modulation was more prominent in participants with the strongest and most T_H2-polarized responses. Downmodulation was observed against Bla g 5 and Bla g 9, the most dominantly recognized allergens in the population study. Furthermore, effective modulation was observed independent of allergen content in the cockroach SCIT extract. Immunodominant responses are effectively modulated by SCIT, and this effect is independent of allergen abundance in the extract utilized for SCIT.