Immune Mechanisms of Allergen-Specific Immunotherapy

Allergen immunotherapy (AIT) has the exclusive ability to modify the natural history of allergy and to maintain its clinical efficacy also after stopping the treatment. This occurs because of the AIT mechanism of action, mainly consist- ing in a specific induction of tolerance to the causative allergen. Such tolerance takes place as a result of a complex inter- action of innate and adaptive immunity processes, that involve inflammatory cells, cytokines and chemokines. The first response to allergens is provided by the antigen-presenting cells, and particularly by dendritic cells (Dcs) that, following activation, acquire chemokine receptors (CCRs), useful for migration to lymphoid organs, where adaptive immune re- sponse is induced. DCs act by presenting the antigen(s) to effectors T cells (T helper CD4 + and T suppressor CD8 +) de- rived from naive T cells. The development of different cell subtypes from naive T cells (Th0) may follow various path- ways and depends on both individual genetic background (atopic/non atopic) and environmental factors. The T cell re- sponse in atopic subjects is influenced by the Th2 polarization promoting the production of cytokines such as IL-4 and IL- 5. On the contrary, the expression of CD80 may determine a Th1 cytokines production, and ICOS-L supports the T- regulatory cells activation that significantly reduce allergic inflammation. The suppressive effect of Treg is due to the ex- pression of high level of the transcription factor Foxp3 on their surface, to the production of IL-10 and TGF-s and to the expression of membrane molecules as CTL-4 PD-1 and BTLA. Recent advances highlighted a role also for Th9 and Th17 lymphocytes. Such immunologic modification leads to the long noted events in studies on mechanisms of action, such as the decrease of specific IgE and the increase of specific IgG1 and IgG4, and ultimately on the inhibition of inflammatory cells such as mast cells, basophils and eosinophils and on the control of clinical symptoms.