Allergen immunotherapy (AIT), also known as desensitization, is one of the few treatments that do more than simply relieve allergy symptoms. It can modify the course of disease by gradually training the immune system to tolerate allergens and, for example, help prevent the progression from allergy to asthma. Researchers at the German Center for Lung Research (DZL), site CPC-M in Munich, have now investigated in detail what happens in the immune system during the first year of treatment. Their findings reveal a critical transitional phase and provide new starting points for improving AIT.
Allergic airway diseases arise from an imbalance in the immune system. Certain T cells drive inflammation, while regulatory T cells normally suppress these responses. Previous studies have shown that many T cells become less active at the beginning of AIT and are considered functionally “exhausted.” The research team aimed to understand this process in greater detail: how does the immune response shift from an inflammation-driven state to a controlled, tolerant condition, and why do some pro-inflammatory cells remain suppressed during therapy?
To address these questions, the researchers combined patient data with experimental models of allergic airway inflammation. They focused on different T cell populations, including classical regulatory T cells (Tregs), Tr17 cells, and pro-inflammatory Th17 cells. Using established laboratory methods, they tracked how these cells change over the course of AIT. In addition, they analyzed patient blood samples using single-cell transcriptomics, which reveals which genes are active in individual cells and allows even subtle changes in cell states to be detected.
The results show a clear shift in immune balance. During AIT, regulatory T cells regain both functional activity and proliferative capacity. The balance between Tr17 cells and classical regulatory T cells also normalizes. In simple terms, the immune system’s “brakes” begin to function more effectively again.
In contrast, Th17 cells remain functionally constrained and are not fully reactivated. In the context of allergic disease, this may be beneficial, as it limits harmful inflammatory responses. After AIT, these cells display a mixed gene expression pattern, reflecting their high plasticity and the complex immune remodeling induced by therapy.
Overall, the findings show that AIT does far more than suppress inflammation. It actively reshapes immune regulation, strengthens regulatory T cell responses, and promotes long-term immune tolerance. At the same time, the persistent alteration of Th17 cell function suggests room for improvement. Targeting these cells more specifically—without disrupting the regulatory environment established by AIT—could further enhance therapeutic efficacy.
This research offers hope for more precise and durable treatments for patients with allergic airway diseases. For clinicians and researchers, it provides a clearer picture of the cellular changes underlying successful allergen immunotherapy and a framework for optimizing immune balance in the future.
Original publication: Charles HS, Gabr AA, Wang SH, Zissler UM, Heine S, Heldner A, Kotz S, Pechtold L, Bonsen LSZ, Pogorelov D, Kau J, Plaschke M, Hills M, Guerth F, Oelsner M, Ohnmacht C, Alessandrini F, Blank S, Chaker AM, Schmidt-Weber CB, Jakwerth CA. TNF Pathway-Mediated Tolerogenic T-Cell Trajectory Driven by Allergen Immunotherapy. Allergy. 2026 Jun;81(6):2184-2197. doi: 10.1111/all.70367. Epub 2026 Apr 30. PMID: 42059108; PMCID: PMC13256266.
