Allergy is a Th2-mediated disease that involves the formation of specific IgE antibodies against innocuous environmental substances. The prevalence of allergic diseases has dramatically increased over the past decades, affecting up to 30% of the population in industrialized countries. The understanding of mechanisms underlying allergic diseases as well as those operating in non-allergic healthy responses and allergen-specific immunotherapy has experienced exciting advances over the past 15 years. Studies in healthy non-atopic individuals and several clinical trials of allergen-specific immunotherapy have demonstrated that the induction of a tolerant state in peripheral T cells represent a key step in healthy immune responses to allergens. Both naturally occurring thymus-derived CD4 1 CD25 1 FOXP3 1 Treg and inducible type 1 Treg inhibit the development of allergy via several mechanisms, including suppression of other effector Th1, Th2, Th17 cells; suppression of eosinophils, mast cells and basophils; Ab isotype change from IgE to IgG4; suppression of inflammatory DC; and suppression of inflammatory cell migration to tissues. The identification of the molecules involved in these processes will contribute to the development of more efficient and safer treatment modalities.Key words: Allergy . Allergen-specific immunotherapy . Tolerance . Treg IntroductionThe immune system is a complex interactive network with the capacity to protect the host from a broad range of pathogens while keeping a state of tolerance to self and innocuous non-self antigens. Immune tolerance-related diseases such as allergy, autoimmunity, tumor tolerance and rejection of organ transplants arise as a direct consequence of dysregulated immune responses. The main clinical manifestations of allergy encompass allergic rhinitis, allergic asthma, food allergy, atopic eczema/ dermatitis and anaphylaxis. Currently, allergen-specific immunotherapy (allergen-SIT) by administration of increasing doses of allergen extracts remains as the single curative treatment of allergic diseases with the potential to modify the course of the disease [1].Adoptive transfer experiments in mouse models of allergy and asthmatic inflammation have shown that Treg are essential for the induction and maintenance of immune tolerance to allergens [2]. In humans, studies on immune responses to allergens in healthy individuals have demonstrated the existence of dominant Treg subsets specific to common environmental allergens [3]. In addition, allergen-SIT represents the only clinically established treatment that induces antigen-specific Treg and peripheral tolerance with the capacity to restore homeostasis in human subjects [3][4][5][6][7][8]. Accordingly, active immune regulation through allergen-specific Treg emerges as a potential therapeutic option 1232Review in the prevention and cure of allergic diseases. The aim of this review is to discuss the immune regulation mechanisms operating in allergic diseases with a focus on the role of Treg in the generation of tolerance agai...

SummaryBackground In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. Objectives To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). Methods In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n = 16), SCIT (n = 16) or pharmacotherapy alone (n = 16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-g, IL-10, and TGF-b secretions were measured. Results SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (Po0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-b (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines.Conclusion Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.

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