Journal of Clinical and Cellular Immunology
Open Access

Cellular Mechanisms of Allergen-Specific Immunotherapy

Charlotte Ava^{* *}Correspondence: Charlotte Ava, Department of Immunology, Harvard University, Massachusetts, USA, Email:

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Description

Allergen-Specific Immunotherapy (AIT) represents a unique and disease-modifying approach to treating allergic disorders such as allergic rhinitis, asthma, and venom allergies. Unlike symptomatic therapies that merely alleviate allergic manifestations, AIT targets the underlying immunological mechanisms of allergy, inducing long-term immune tolerance to specific allergens. The clinical efficacy of AIT, whether administered subcutaneously or sublingually however, its cellular and molecular mechanisms remain a vibrant area of research. Understanding these mechanisms is crucial not only for optimizing current therapies but also for developing novel approaches that are safer, more effective, and personalized.

AIT operates at the cellular level by reshaping the immune response from a pathologic type 2 helper T cell-dominated profile, characteristic of allergic reactions, toward a regulatory or non-inflammatory phenotype. In allergic individuals, exposure to allergens triggers Dendritic Cells (DCs) to present allergenderived peptides to naive T cells, promoting differentiation into Th2 cells. These Th2 cells release cytokines such as interleukin-4 (IL-4), IL-5, and IL-13, which drive IgE production by B cells, eosinophil recruitment, and mast cell sensitization. In contrast, AIT redirects this pathway by inducing the generation of allergen-specific regulatory T cells (Tregs) and regulatory B cells (Bregs), leading to suppression of Th2-mediated responses and the establishment of immune tolerance.

Role of dendritic cells and regulatory t cells in ait

Dendritic cells are central orchestrators of AIT-induced immune modulation. During AIT, repeated controlled exposure to allergens promotes the differentiation of tolerogenic DCs, which exhibit low expression of co-stimulatory molecules and produce immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta. These tolerogenic DCs preferentially drive naive T cells toward a Treg phenotype, characterized by expression of FOXP3 and secretion of IL-10. These cytokines play a dual role: they suppress effector Th2 cell function and inhibit IgE synthesis by B cells, while simultaneously enhancing the production of non-inflammatory IgG4 antibodies.

The induction of Tregs is pivotal to AIT’s success. Allergenspecific Tregs act locally in the tissues and systemically in the circulation, suppressing allergen-induced mast cell degranulation and eosinophil infiltration. Their suppressive effects also extend to other effector T-cell subsets, including Th1 and Th17 cells, ensuring a broad immunoregulatory environment. Moreover, Tregs contribute to a long-lasting “immune memory” of tolerance, which explains why the clinical benefits of AIT often persist for years after treatment cessation. Emerging evidence also highlights the role of tissue-resident memory Tregs in the nasal mucosa and lungs as key mediators of localized immune tolerance during AIT.

B cells, antibodies, and the humoral shift

Another crucial aspect of AIT’s cellular mechanisms involves allergen-specific B cells and the humoral immune response. In allergic individuals, allergen exposure favors class-switch recombination toward IgE production, which binds mast cells and basophils, sensitizing them for rapid allergic reactions. AIT redirects this process by promoting the expansion of Bregs and inducing the production of IgG4 antibodies, which compete with IgE for allergen binding. IgG4 antibodies function as “blocking antibodies,” preventing allergen-mediated cross-linking of IgE on effector cells, thereby inhibiting histamine release and downstream inflammatory responses.

Bregs themselves contribute to immune tolerance by producing IL-10 and TGF-β, reinforcing the suppressive milieu established by Tregs. This cross-talk between regulatory B and T cells amplifies immunomodulation and stabilizes the noninflammatory state. Additionally, AIT has been shown to decrease the frequency and activity of allergen-specific memory B cells that are skewed toward IgE production, further consolidating the therapeutic effects of the intervention.

The interplay between cellular and humoral mechanisms explains why AIT not only alleviates symptoms but also modifies the natural course of allergic disease. It is now understood that the clinical efficacy of AIT depends on a delicate balance between effector cell suppression, regulatory cell induction, and antibody class switching a triad that is finely orchestrated over months to years of therapy.

Conclusion

Allergen-specific immunotherapy exemplifies a paradigm shift in the management of allergic diseases, moving from symptomatic relief toward disease modification through immune tolerance. At the cellular level, AIT reshapes the immune landscape by promoting tolerogenic dendritic cells, inducing allergen-specific Tregs, and expanding regulatory B cells, all of which suppress Th2-mediated inflammation. Concurrently, the humoral response is redirected toward IgG4 production, which neutralizes allergens and prevents IgE-mediated hypersensitivity. This coordinated modulation of cellular and humoral immunity explains the long-lasting clinical benefits of AIT and underscores its potential as a model for precision immunotherapy. Continued research into these mechanisms may pave the way for more efficient, safer, and shorter-duration treatment regimens, ultimately improving outcomes for individuals living with allergic disorders.