T-cell Responses
Successful SCIT in patients with grass pollen[86] and with mite[73] allergy has been shown to be accompanied by increased production of IL-10 in allergen-stimulated peripheral T-cell cultures. In one study, this was accompanied by suppression of allergen-induced T-cell proliferation, possibly mediated by CD4+CD25+ T cells and inhibited by strategies that blocked IL-10 or TGF-β.[73] In addition, SCIT has been associated with alterations in peripheral T-cell responses, with immune deviation in favor of Th1 responses.[87] However, changes in T-cell responses to allergen have not been universally observed in cells derived from peripheral blood.[88,89]
Studies demonstrating that SLIT is able to induce Tregs in clinical practice are emerging in recent years. Nevertheless, a preliminary study demonstrated that compared with untreated controls, SLIT increased IL-10 production in peripheral blood mononuclear cells from patients with HDM allergy following in vitro stimulation with Dermatophagoides antigens, as well as recall antigens such as Candida albicans or phytohemaglutinin.[69] In another study in childhood asthma with HDM allergy, 6 and 12 months of SLIT downregulated specific IgE response, while slightly increasing specific IgA.[72]
A 12-month DBPC study of HDM-SLIT was performed demonstrating decreased CD4+ T-cell proliferation and IL-5 production along with increased IL-10 secretion and specific IgG4 in the active group. Treg (CD4+CD25+CD127lo/Foxp3+) function was demonstrated by suppression of allergen-specific effector T-cell proliferation and cytokine production. This was the first study demonstrating TGF-β-mediated immunological suppression of SLIT.[90]
Local changes in the nasal mucosa have been measured after SCIT. These include skewing of cytokine profiles in favor of Th1 responses[91,92] and the local induction of Tregs with increases in IL-10[82] and TGF-β.[84] Using triple immunofluorescence microscopy, increases in CD3+CD25+Foxp3+ phenotypic Tregs have been demonstrated in the nasal mucosa after successful grass pollen immunotherapy, with further increases after immunotherapy detected during natural allergen exposure during the pollen season.[93]
Immunotherapy. 2011;3(6):747-756. © 2011 Future Medicine Ltd.
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