Insect allergyAre regulatory T cells the target of venom immunotherapy?Jutel, Mareka,b; Akdis, Mübeccela; Blaser, Kurta; Akdis, Cezmi AaAuthor Information aSwiss Institute of Allergy and Asthma Research, Davos, Switzerland bDepartment of Internal Medicine and Allergology, Wrocław Medical University, Wrocław, Poland Correspondence to Dr Cezmi A. Akdis, Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH7270 Davos, Switzerland Tel: +41 81 4100848; fax:+41 81 4100840; e-mail: [email protected] Current Opinion in Allergy and Clinical Immunology: August 2005 - Volume 5 - Issue 4 - p 365-369 doi: 10.1097/01.all.0000173784.81024.7a Buy Metrics Abstract Purpose of review Allergen-specific immunotherapy is the only treatment that leads to lifelong tolerance to previously disease-causing allergens by restoring normal immunity against allergens. T-regulatory (TReg) cells are involved in preventing sensitization to allergens and represent a major target for venom- or other allergen-specific immunotherapy. Recent findings Induction of peripheral tolerance in T cells, which is characterized mainly by suppressed proliferative and cytokine responses against the T-cell epitopes of major allergens, is an essential step in specific immunotherapy. It is initiated by the autocrine action of interleukin-10 and/or transforming growth factor-β, which are produced by antigen-specific TReg cells. Tolerized T cells can be reactivated to produce distinct T-helper-1 or T-helper-2 cytokine patterns, thus directing allergen-specific immunotherapy toward successful or unsuccessful outcomes. TReg cells directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. In addition, there is accumulating evidence that they may suppress IgE production and induce IgG4 and IgA production against allergens. In addition, histamine released from mast cells and basophils may efficiently contribute to immunoregulation during specific immunotherapy, and affect TReg cells and the production of their cytokines via histamine receptor 2. Summary By applying recent knowledge in TReg-cell-dependent mechanisms of peripheral tolerance, more rational and safer approaches to the prevention and cure of venom hypersensitivity may be developed in the future. © 2005 Lippincott Williams & Wilkins, Inc.