Interleukin-10, T regulatory cells and specific allergy treatment

Allergen-specific immunotherapy (SIT) is efficiently used in allergy to insect venoms and allergic rhinitis [1, 2]. Currently, it represents the only curative approach for type I allergy. A rise in allergen-blocking IgG antibodies, particularly of the IgG4 class, and a reduction in mast cell and eosinophil numbers including the release of mediators were shown to be associated with successful SIT [3-5]. Furthermore, SIT was found to be associated with a decrease in IL-4 and IL-5 production by CD4(+) T cells [6, 7]. However, it is now clear that the induction of peripheral tolerance in antigen-specific T cells and increased production of IL-10 and/or TGF-beta is essential for successful SIT [8-10]. Similar to SIT with whole allergens, injection of minimal length T cell peptides of bee venom phospholipase A(2) (PLA) or peptides of the cat allergen Fel d 1, showed specific tolerance in peripheral T cells [11-13]. T cells predominantly secreting IL-10 are termed T-regulatory 1 cells (Tr1) [14]; those producing TGF-beta T cells are termed Th3 cells [15]. Apparently, both IL-10 and TGF-beta cooperate in peripheral T cell tolerance to mucosal allergens. House dust mite (HDM) allergens represent typical aero-allergens, which preferentially interact with the mucosal immune system. The changes in T cell response to Der p1, the major HDM allergen, were investigated during the first 70 days of SIT with whole allergen extract [16]. Within this time the suppressive cytokines IL-10 and TGF-betasignificantly increased, whereas allergen-induced T cell proliferation and IL-5, IL-13 and IFN-gamma secretion substantially decreased. It was found that SIT generates regulatory T cells of the CD4(+) CD25(+) type, which secrete IL-10 and TGF-beta and specifically suppress allergen-induced responses [16]. In contrast, the CD4(+) CD25(+) T cells taken before therapy did not display such suppressive properties. Thus, allergen-specific T regulatory cells (T-reg) represent a fraction of the peripheral CD4(+) CD25(+) T cell population and secrete IL-10 and/or TGF-beta.