da Silva Antunes Ricardo, Sutherland Aaron, Abawi Adam, Frazier April, Pomés Anna, Glesner Jill, Slater Jay E, Mindaye Samuel T, Cho Kate, Zhou Grace, Ozanne Marie V, Calatroni Agustin, Visness Cynthia M, Altman Matthew C, Wood Robert A, O'Connor George T, Pongracic Jacqueline A, Khurana Hershey Gurjit K, Kercsmar Carolyn M, Gruchalla Rebecca S, Gill Michelle, Searing Daniel, Liu Andrew H, Zoratti Edward, Kattan Meyer, Busse Paula J, Sheehan Will, Bacharier Leonard B, Teach Stephen J, Wheatley Lisa M, Togias Alkis, Busse William W, Jackson Daniel J, Sette Alessandro
Division of Vaccine Discovery La Jolla Institute for Immunology, La Jolla, Calif.
Basic Research, InBio, Charlottesville, Va.
J Allergy Clin Immunol. 2025 Jul 24. doi: 10.1016/j.jaci.2025.07.011.
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 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.
Immunodominant responses are effectively modulated by SCIT, and this effect is independent of allergen abundance in the extract utilized for SCIT.
在皮下过敏原免疫疗法（SCIT）中，T细胞对过敏原提取物各个成分的反应尚未完全阐明。具体而言，尚不清楚T细胞对免疫显性过敏原的反应对调节的敏感性是更高还是更低，以及免疫疗法提取物中过敏原的丰度是否会影响T细胞反应调节。
为填补这些空白，我们在双盲、安慰剂对照、多中心的CRITICAL（NCT03541187）SCIT试验中评估了对每种主要蟑螂过敏原具有特异性的CD4 T细胞反应性。
年龄在8至17岁、患有轻度至中度且控制良好的哮喘的参与者接受了12个月的蟑螂SCIT治疗（n = 20）或安慰剂治疗（n = 26）。在治疗12个月前后分离外周血单核细胞。使用源自11种明确的蟑螂过敏原的重叠肽池以及用于检测白细胞介素-4、干扰素-γ和白细胞介素-10产生的细胞内细胞因子染色，评估基线和治疗后的CD4 T细胞反应。评估T细胞反应的强度、细胞因子极化、过敏原免疫显性以及与蟑螂SCIT提取物中过敏原含量的相关性。
SCIT调节在具有最强和最T2极化反应的参与者中更为显著。观察到针对人群研究中最主要识别的过敏原Bla g 5和Bla g 9的下调。此外，观察到有效的调节与蟑螂SCIT提取物中的过敏原含量无关。
免疫显性反应可被SCIT有效调节，且这种效应与SCIT所用提取物中的过敏原丰度无关。
