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