Tolerance mechanisms in allergen immunotherapy

Abstract

Purpose of review Allergen immunotherapy is the only treatment modality which alters the natural course of allergic diseases by restoring immune tolerance against allergens. Deeper understanding of tolerance mechanisms will lead to the development of new vaccines, which target immune responses and promote tolerance. Recent findings Successful allergen immunotherapy (AIT) induces allergen-specific peripheral tolerance, characterized mainly by the generation of allergen-specific Treg cells and reduction of Th2 cells. At the early phase, AIT leads to a decrease in the activity and degranulation of mast cells and basophils and a decrease in inflammatory responses of eosinophils in inflamed tissues. Treg cells show their effects by secreting inhibitory cytokines including interleukin (IL)-10, transforming growth factor-β, interfering with cellular metabolisms, suppressing antigen presenting cells and innate lymphoid cells (ILCs) and by cytolysis. AIT induces the development of regulatory B cells producing IL-10 and B cells expressing allergen-specific IgG4. Recent investigations have demonstrated that AIT is also associated with the formation of ILC2reg and DCreg cells which contribute to tolerance induction. Summary Research done so far, has shown that multiple molecular and cellular factors are dysregulated in allergic diseases and modified by AIT. Studies should now focus on finding the best target and ideal biomarkers to identify ideal candidates for AIT.

PD-L1 Blockade During Allergen Sensitization Inhibits the Synthesis of Specific Antibodies and Decreases Mast Cell Activation in a Murine Model of Active Cutaneous Anaphylaxis

“…We can speculate that blockade of this immunomodulatory pathway could result in reduced regulatory cell function, aggravating pre-existing inflammatory diseases. An active search for regulatory T cell induction is ongoing through allergen-specific immunotherapy for allergic diseases (31). A recent clinical trial with patients allergic to peach subjected to sublingual immunotherapy showed that the expression of PD-L1 by peripheral-blood monocytes increased in the treated group, suggesting a role for this pathway in allergen tolerance induction (32).…”

COVID-19 vaccination and allergen immunotherapy (AIT) - A position paper of the German Society for Applied Allergology (AeDA) and the German Society for Allergology and Clinical Immunology (DGAKI)

“…AIT attempts to induce a tolerogenic response to an individual antigen dose by continuous administration of that antigen. The main mechanisms include early desensitization of effector cells and progressive onset of a regulatory B and T cell response [ 34 , 35 , 36 ]. Although the main changes of specific immunotherapy are antigen-specific, recent data support a beneficial effect in restoring the general balance of the immune system altered toward Th2 immune response [ 37 , 38 ].…”

Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy

“…Tolerance of allergens by peripheral T cells seems crucial to a normal immune response. The immune regulatory response involves a complex system, which includes multiple populations of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), Natural Killer (NK) cells, immunosuppressive plasmocytes (ISPCs), and a regulatory subset of ILCs with interconnected functions that are currently being studied extensively [ 3 , 6 , 7 , 8 ]. Within this complex system, there are also subtypes of T cells with immunosuppressive function generically referred to as regulatory T cells (Tregs), wich have been described in humans, and play a fundamental role in allergen tolerance.…”

“…Also, our group demonstrated the involvement of regulatory mechanisms in the response to olive pollen, specifically a decrease in TGF-β and Foxp3 in patients allergic to olive pollen during the period of high pollen exposure and a recovery of the regulatory response, in allergic patients treated with specific immunotherapy to this pollen [ 24 ]. In fact, one of the most extensively studied parameters to determine tolerance induction during allergen-immunotherapy consists of monitoring the increase in Tregs during immunotherapy treatments [ 7 ].…”