Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1 : Th2 cytokine ratios

Abstract

SUMMARYGrass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term bene®t. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in In contrast, there were no signi®cant changes in peripheral T-cell proliferative responses or cytokine production for IFN-c or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-c to IL-5 mRNA + cells in the nasal mucosa, whereas these changes were not re¯ected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.

CD4+ T Cell-Specific Deletion of IL-4 Receptor α Prevents Ovalbumin-Induced Anaphylaxis by an IFN-γ-Dependent Mechanism

“…Interestingly, successful allergen-specific immunotherapy in humans is often associated with increased IFN-␥ and IL-10, rather than a decrease in Th2 cytokines (44,45), and tolerance to food allergens has been associated with high levels of IFN-␥ (46). Treatment of atopic dermatitis with rIFN-␥ has improved rhinitis and conjunctivitis in patients with concurrent symptoms (47).…”

The IgE-facilitated allergen binding (FAB) assay: Validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses

“…The mechanisms that are associated with successful immunotherapy involve both Tand B-cell mediated events . Cellular changes include immune deviation favouring T helper (Th) 1 responses (Wachholz et al, 2002), and the induction of regulatory cells producing interleukin (IL)-10 (Francis et al, 2003). Treatment is associated also with the induction of allergen-specific serum IgG4 antibodies (Gehlhar et al, 1999;Jutel et al, 2003;Nouri-Aria et al, 2004).…”

Allergy Vaccine Engineering: Epitope Modulation of Recombinant Bet v 1 Reduces IgE Binding but Retains Protein Folding Pattern for Induction of Protective Blocking-Antibody Responses

“…Studies based on T cells derived from peripheral blood show ambiguous results; some studies find a reduction in the production of Th2 cytokines combined with a reduction in allergen-specific stimulation (15), i.e., tolerance induction, whereas other studies find a reduction of the Th2 phenotype, but not a reduction in stimulation (16). Other studies demonstrate a reduction in Th2 cytokine production accompanied by an increase in Th1 cytokine production (17,18), i.e., immune deviation, whereas yet other studies fail to demonstrate a reduction of the Th2 phenotype in PBMC (13,19). Recently, a mechanism based on the induction of allergen specific CD4 ϩ CD25 ϩ regulatory T cells has been proposed, a mechanism resulting in the production of IL-10 and TGF-␤ and a down-regulation of Th1 as well as Th2 allergen-specific T cell responses (20).…”

“…Recently, a mechanism based on the induction of allergen specific CD4 ϩ CD25 ϩ regulatory T cells has been proposed, a mechanism resulting in the production of IL-10 and TGF-␤ and a down-regulation of Th1 as well as Th2 allergen-specific T cell responses (20). The ambiguity of these observations may be due to the fact that the active cells of the allergic immune response are physically located in the airway mucosa, and that changes in T cell phenotypes are not properly reflected in the circulation (19).…”