T-cell subset changes during the first year of pre-seasonal allergoid allergen-specific immunotherapy

Allergen-specific immunotherapy (AIT) is the only treatment for type I allergy, which achieves long-lasting effects. Repeated subcutaneous applications of allergen extracts cause a protective antibody response and an immune deviation of T cells. In AIT with allergoids, chemically modified allergen extracts are injected. During a so-called special pre-seasonal application scheme, after the initial phase of applying increased doses of allergoids is followed by natural allergen exposure as a maintenance phase. The effectiveness of allergoid vaccines has been described regarding the improvement of clinical symptoms and the development of protective humoral responses. In this longitudinal observational study, we sought to investigate changes at the T cell level in pre-seasonal AIT with allergoid. Different subsets within CD4⁺ and CD8⁺ T cells were monitored by flow cytometry in PBMC of patients known to possess protective antibody responses. Compared to before treatment, a small early boost among allergenic Th cells was observed after 4 months of AIT. In line, a slight Th2 bias was observed after 4 months within circulating T follicular T cells, Tfh and Tfc, representing pre-existing memory Th2 cells. Furthermore, it was demonstrated that responsiveness of CD8⁺ T cells to allergen stimulation decreased during the course of treatment. Apart from that, we found an influence of the meteorological season on the activation profile of Tfh and Tfc over the course of the treatment. Together, this is the first study investigating changes of different T cell subsets over the course of an allergoid AIT against airborne allergens. Our findings match previous reports on conventional AIT, especially the initial increase of Th2 responses. However, the observed changes were less pronounced which may be either due to the modification of allergens or to the reduced maintenance dose provided by natural allergen exposure compared to a perennial protocol.