Anaphylaxis: Are Regulatory T Cells the Target of Venom Immunotherapy?
The immunological mechanism of venom immunotherapy (VIT) was unclear for a long time. VIT has been demonstrated to influence the deviated immune response in allergic individuals in a specific manner and eventually redirect the immune system towards normal immunity. A rise in allergen-blocking IgG antibodies, particularly of the IgG4 class, which supposedly block allergen and IgE-facilitated antigen presentation , the generation of IgE-modulating CD8 + T cells  and a reduction in the numbers of mast cells and eosinophils, including the release of mediators [3, 4] were shown to be associated with successful allergen-specific immunotherapy (SIT). Later on, SIT was found to be associated with a decrease in IL-4 and IL-5 production by CD4+ T helper (Th) 2 cells [5, 6], and in some experimental conditions with a shift towards increased IFN-γ production [7–9]. Distinct Th1 and Th2 subpopulations of T cells counter-regulate each other and play a role in distinct diseases . The mechanism of repolarization of specific T cell activity from dominating Th2-type towards Th1-type, as observed during VIT had been a matter of controversy. A new light was shed when a further subtype of T cells, with immunosuppressive function and cytokine profiles distinct from either Th1 and Th2 cells, termed regulatory/ suppressor T cells (TReg) has been described [11, 12]. The evidence for their existence in humans has been demonstrated [13, 14]. In addition to Th1 cells, TReg cells are able to inhibit the development of allergic Th2 responses and play a major role in allergen-SIT [13, 15] (Fig. 1). Recent studies have also demonstrated that peripheral T-cell tolerance is crucial for a healthy immune response and successful treatment of allergic disorders [13– 15]. The crucial role of TReg cells in the induction of allergen-specific peripheral tolerance during VIT has been well documented. Thus, the basis for new developments in SIT has been created.
KeywordsSpecific Immunotherapy Venom Immunotherapy Normal Immunity Healthy Immune Response Honeybee Sting
Unable to display preview. Download preview PDF.
- 14.Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H, Kegel C, Disch R, Schmidt-Weber CB, Blaser K, Akdis CA: Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J. Exp. Med. 2004;199:1567–1575CrossRefPubMedGoogle Scholar
- 18.Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, Akdis AC: A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apop-tosis release IP-10, Mig and iTac for T cell chemotaxis towards epidermis in atopic dermatitis. J. Immunol. 2003;171:1078–1084PubMedGoogle Scholar
- 52.Müller UR, Jutel M, Reimers A, Zumkehr J, Huber C, Kriegel C, Steiner U, Haeberli G, Akdis M, Helbling A, Schnyder B, Blaser K, Akdis C. Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy. J. Allergy Clin. Immunol. 2008;122:1001–1007CrossRefPubMedGoogle Scholar