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

Background: 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.

Objective: 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.

Methods: 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.

Results: SCIT modulation was more prominent in participants with the strongest and most T2-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.

Conclusion: Immunodominant responses are effectively modulated by SCIT, and this effect is independent of allergen abundance in the extract utilized for SCIT.