IL‐10 and TGF‐β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy

Jutel, Marek; Akdiş, Mübeccel; Budak, Ferah; Aebischer-Casaulta, Carmen; Wrzyszcz, M; Blaser, Kurt

doi:10.1002/eji.200322919

Cited by 827 publications

(792 citation statements)

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“…Patients receiving allergen-specific immunotherapy have been shown to have increased concentrations of allergen-specific IgG4 antibodies in their serum (Gehlhar et al, 1999;Jutel et al, 2003;Nouri-Aria et al, 2004;Djurup et al, 1987). However assays that detect only immunoreactive IgG4 are unlikely to predict clinical efficacy (Djurup et al, 1987;Muller et al, 1989;Ewan et al, 1993;Bodtger et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…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). IgG4 antibodies are thought to have blocking activities as they compete with IgE for binding to mast cells, basophils and other IgE receptor-expressing cells (Garcia et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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

Shamji

Wilcock

Wachholz

et al. 2006

Journal of Immunological Methods

132

129

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The IgE-Facilitated Allergen Binding (IgE-FAB) assay represents an in vitro model of facilitated allergen presentation. Allergen-IgE complexes are incubated with an EBV-transformed B-cell line and complexes bound to CD23 on the surface of cells are detected by flow cytometry. Addition of serum from patients who have received allergen-specific immunotherapy has been shown previously to inhibit allergen-IgE complex binding to CD23 on B cells.In this study, we describe the characterisation and analytical validation of the grass pollen-specific IgE-FAB assay according to guidelines from the International Conference on Harmonisation. We established the intra and inter -assay variability of IgE-FAB and have defined the detection limits of this assay. We have also demonstrated assay linearity and robustness. Using results from a randomised double-blind placebo controlled trial of grass pollen immunotherapy (n=33), we have defined the clinical sensitivity and specificity of the IgE-FAB assay using ROC curve analysis.In conclusion, the IgE-FAB assay is reproducible, robust, sensitive and specific method suitable as a tool for monitoring inhibitory antibody function from patients receiving allergen immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Shamji

Wilcock

Wachholz

et al. 2006

Journal of Immunological Methods

132

129

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“…The establishment of long-term tolerance upon immunotherapy to aeroallergens is highlighted by the increase of allergen-specific IL-10/TGF-b producing FoxP3 ? Treg (Francis et al 2003;Ling et al 2004) and the shift in the ratio of Th2/Th1 type cytokines (Faith et al 2003;Jutel et al 2003). In egg and peanut allergies, OIT protocols have been reported with an in vitro increase of FoxP3 ?…”

Section: Mechanisms Of Oit In Food Allergymentioning

confidence: 99%

Food Allergy and the Oral Immunotherapy Approach

Cabrera

Urra

2014

Arch. Immunol. Ther. Exp.

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Food allergy represents an increasing health problem, with children being the most affected population. The symptoms can appear within minutes or hours of ingesting the offending food, producing skin manifestations, respiratory, gastrointestinal and anaphylactic reactions in the severe forms. Food allergy is established by the loss of tolerance to food proteins, and is characterized by an altered balance of regulatory T (Treg) cells and the shift to Th2 type cytokines in the intestinal lamina propria. We have described the contribution of different factors in establishing oral tolerance, such as the antigenic exposition route, the gut microenvironment, and the timing of the food introduction. Apart from avoiding the food, immunotherapy is the only intervention which produces oral desensitization to food proteins. Among the underlying immunological mechanisms of oral immunotherapy (OIT) are the changes in humoral immunity (a decrease of allergen-specific IgE and an increase of allergen-specific IgG4) and cellular changes such as the increased number of FoxP3 ? Treg cells. At present, the experiences of OIT with various foods are offering promising results. OIT appears to be safe producing low adverse reactions, and effective in inducing desensitization in most subjects with food allergy.

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“…Treg, particularly for the thymic-derived CD4 1 CD25 1 Treg, express the Foxp3 gene and mediate the suppressive function in an antigen-non-specific manner [40,41]. The expression of Foxp3 gene has reported to be induced via IL-10 or TGF-b in the population of CD4 1 CD25 À T cells and leads to develop the Tr1 cells in vitro [42].…”

Section: Discussionmentioning

confidence: 99%

“…Although many aspects of the mechanisms by which the regulatory cells function remain to be elucidated, it has been well established that Treg use both cell-to-cell interactions and/or the production of 34,38,39]. Treg, particularly for the thymic-derived CD4 1 CD25 1 Treg, express the Foxp3 gene and mediate the suppressive function in an antigen-non-specific manner [40,41]. The expression of Foxp3 gene has reported to be induced via IL-10 or TGF-b in the population of CD4 1 CD25 À T cells and leads to develop the Tr1 cells in vitro [42].…”

mentioning

confidence: 99%

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

et al. 2008

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Asthma is a chronic inflammatory disorder caused by T-cell-mediated inflammation within airways. No antigen-specific treatment has been available. Using an OVA-induced murine asthma model, we find that co-immunization of an OVA epitope peptide with a DNA vaccine encoding the same epitope is able to prevent this experimental asthma as evidenced in the marked reduction of infiltrations of eosinophils and lymphocytes into the site of the allergen challenge. We demonstrate that the prevention of experimental asthma was directly related to the induction of a population of OVA-specific T-regulatory cells (Treg) exhibiting a CD4 1 CD25 À FoxP3 1 phenotype and expressing IL-10, TGF-b and IFN-c following the co-immunization. Blockade of IL-10 and TGF-b of the Treg by anti-IL-10 and TGF-b antibodies is partially able to reverse the suppression in vitro and in vivo, which caused the recurrence of the inflammation. Furthermore, adoptive transfer of the induced Treg is also able to suppress the OVA-induced asthma. To our knowledge, the combination of peptide with its cognate DNA vaccine protect experimental asthma via the induced epitope-specific Treg has not been previously reported and such strategy may lead to a novel immunotherapy against asthma in humans.Key words: Asthma Á Immune regulation Á Tolerance Á Treg cell Á Vaccination IntroductionAsthma is a chronic inflammatory disorder of the airways characterized by airway obstruction, increased airway responsiveness to a variety of stimuli as well as the infiltration by many inflammatory cells, including eosinophils, macrophages, lymphocytes and mast cells into lung tissue. CD4 1 T cells and Th2-biased cytokines (i.e. IL-4, IL-5 and IL-13) are believed to play a central role in the initiation and maintenance of the asthmatic response by regulating the production of IgE and the differentiation, recruitment and activation of mast cells and eosinophils [1][2][3].It has been proposed that Th1 cells, which secrete interferon-g (IFN-g), could protect against allergic disease by inhibiting the proliferation and development of Th2 cells [4] and IgE production [5]. Approaches of redirecting immunity from a Th2 type to Th1 type have also been demonstrated to result in temporary reduction of allergic reactions [6]. However, both autoimmune disease [7] and pathogen infection [8] induced Th1-biased immune responses were found to reduce the likelihood of allergy disease. Hansen et al. demonstrated that antigen-specific Th1 cells were ineffective in reducing the airway hyper-reactivity induced by Th2 cells but caused serious airway inflammation [9]. Thus, immunotherapeutic approaches using Th1 cell responses against asthma are rather complicated.Besides redirecting immunity-based approaches, several other strategies have also been considered to reduce allergic responses, including non-specific immunosuppressive drugs or monoclonal [21,22]. In this report, we further demonstrated that co-immunization of DNA and peptide vaccines against the same epitope-sequence of ovalbumin (OVA, aa 323...

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IL‐10 and TGF‐β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy

Cited by 827 publications

References 60 publications

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

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

Food Allergy and the Oral Immunotherapy Approach

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

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