Role of interleukin 10 in specific immunotherapy.

Akdiş, Cezmi A.; Blesken, Thorsten; Akdiş, Mübeccel; Wüthrich, B; Blaser, Kurt

doi:10.1172/jci2250

Cited by 882 publications

(915 citation statements)

References 62 publications

Supporting

Mentioning

846

Contrasting

Unclassified

Order By: Relevance

“…Specific immunotherapy (SIT) has been shown to induce durable immunological changes in response to the allergen, through generating neutralizing antibodies, through suppressing numbers and activity of allergen‐specific Th2 cells and type 2 innate lymphoid cells (ILC2s), and by inducing regulatory T‐cell activity 2. Successful SIT has been associated with enhanced release of IL‐10 in PBMC cultures restimulated with allergen,3 serum‐dependent suppression of cross‐presentation by B cells,4 and selective loss of those T‐cell clones with allergen‐epitope specificities that are increased in atopic individuals compared to healthy controls 5, 6. Specific immunotherapy (SIT) induces long‐term tolerance to the allergen, as evidenced by the absence of allergic manifestations upon repeated allergen challenges 1…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Hesse

Ieperen

Habraken

et al. 2018

Allergy

View full text Add to dashboard Cite

BackgroundAllergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment.AimsHere, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)‐driven mouse model of allergic asthma.Materials and methods HDM‐sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen‐induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue.Results ESR measurement shows suppression of early allergic response in HDM‐SCIT– and DerP1/2‐SCIT–treated mice. Both HDM‐SCIT and DerP1/2‐SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2‐SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2‐SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL‐33, CCL17 and eotaxin levels in lung tissue.DiscussionTaken together, these data show that purified DerP1/2‐SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM‐induced activation of lung structural cells including airway epithelium.ConclusionsWe postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.

show abstract

Section: Introductionmentioning

confidence: 99%

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Hesse

Ieperen

Habraken

et al. 2018

Allergy

View full text Add to dashboard Cite

show abstract

“…Accordingly, it may be expected that the use of Api m (1/2/3) may lead to stimulation of memory Th2 responses. However, the induction of specific peripheral T cell tolerance and efficiently decreased Th2 cytokines has been demonstrated both in conventional BV immunotherapy [19] and Api m 1 peptide immunotherapy [20] as well as healthy immune response to allergens [21], which might be more relevant in the present study for the prevention of IgE as well as IgG1 and IgG2a after native allergen exposure.…”

Section: Discussionmentioning

confidence: 82%

“…PBMC were isolated by Ficoll (Biochrom, Berlin, Germany) density gradient centrifugation of peripheral venous blood and stimulated with titrated equimolar amounts of Api m 1, Api m 2, Api m 3 and Api m (1/2/3) as described [19,28]. The stimulation index was calculated as the quotient of counts per minutes obtained by allergen-stimulated PBMC and unstimulated PBMC.…”

Section: Human T Cell Culturesmentioning

confidence: 99%

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Karamloo¹,

Schmid‐Grendelmeier

Kussebi³

et al. 2005

Eur. J. Immunol.

View full text Add to dashboard Cite

Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A 2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FceRI cross-linking in sensitized individuals.

show abstract

“…However in this study, we identify the T cell with a phenotypic resemblance to Tr1 of CD4 À /CD25 À /Foxp3 1 /IL-10 1 /IFN-g/TGFb 1 after the induction of co-immunization with DNA and protein protocol, this Tr1 like cells can successfully suppress the development of asthma-like inflammations in an antigen-specific manner in mice. 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].…”

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 IL-10 and TGF-b [33,34,38,39]. 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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

View full text Add to dashboard Cite

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...

show abstract

Role of interleukin 10 in specific immunotherapy.

Cited by 882 publications

References 62 publications

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

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

Contact Info

Product

Resources

About