Are regulatory T cells the target of venom immunotherapy?
OBJECTIVE
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.


RESULTS
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-beta, 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.


CONCLUSIONS
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.
Jutel
Marek
M
Swiss Institute of Allergy and Asthma Research, Davos, Switzerland.
Akdis
Mübeccel
M
Blaser
Kurt
K
Akdis
Cezmi A
CA
D000818:Animals; D001514:Bee Venoms / Q000009:adverse effects / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000187:drug effects / Q000378:metabolism; D007299:Insect Bites and Stings / Q000276:immunology* / Q000628:therapy; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
D001514:Bee Venoms; D007074:Immunoglobulin G; D007073:Immunoglobulin E