Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model

Vissers, Joost L. M.; Esch, Betty C.A.M. van; Hofman, Gerard A.; Kapsenberg, Martien L.; Weller, F. R.; Oosterhout, Antoon J. M. van

doi:10.1016/j.jaci.2004.02.041

Cited by 75 publications

(69 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Subcutaneous delivery of three high-dose (1 mg) OVA injections was shown to suppress asthma manifestations as efficiently as the gradual updosing of OVA in the mouse model (18). The suppressive effects on asthma manifestations were found to last for $5 wk after IT treatment and to be dependent on IL-10 production (19). Moreover, IT treatment also induces increased serum levels of OVA-specific IgG and IgA Abs, mirroring the observations in human subjects.…”

mentioning

confidence: 53%

Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

Shirinbak

Taher

Maazi

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Allergen-specific immunotherapy (IT) uniquely renders long-term relief from allergic symptoms and is associated with elevated serum levels of allergen-specific IgG and IgA. The allergen-specific IgG response induced by IT treatment was shown to be critical for suppression of the immediate phase of the allergic response in mice, and this suppression was partially dependent on signaling through FcγRIIB. To investigate the relevance of the allergen-specific IgG responses for suppression of the Th2-driven late-phase allergic response, we performed IT in a mouse model of allergic asthma in the absence of FcγRIIB or FcγRI/FcγRIII signaling. We found that suppression of Th2 cell activity, allergic inflammation, and allergen-specific IgE responses is independent of FcγRIIB and FcγRI/FcγRIII signaling. Moreover, we show that the IT-induced allergen-specific systemic IgG or IgA responses and B cell function are dispensable for suppression of the late-phase allergic response by IT treatment. Finally, we found that the secretory mucosal IgA response also is not required for suppression of the Th2-driven allergic inflammation by IT. These data are in contrast to the suppression of the immediate phase of the allergic response, which is critically dependent on the induced allergen-specific serum IgG response. Hence, IT-induced suppression of the immediate and late phases of the allergic response is governed by divergent and independent mechanisms. Our data show that the IT-induced suppression of the Th2 cell-dependent late-phase allergic response is independent of the allergen-specific IgG and IgA responses that are associated with IT treatment.

show abstract

mentioning

confidence: 53%

Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

Shirinbak

Taher

Maazi

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Different previous studies have demonstrated that depletion of IL-10 signaling in a mouse model of IT leads to abrogation of IT-mediated suppression (26,52). In the current study, we could extend these results in a chronic model of allergic airway disease that resembles more closely the human situation when compared with prophylactic models mostly used.…”

Section: Discussionmentioning

confidence: 89%

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

Böhm

Maxeiner

Meyer-Martin

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell–mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet–expressing Th1 cells, T cell–derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3+ regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3+, and IL-10–producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3+ Treg cells, thymic Foxp3+ Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

show abstract

“…Airway responses were expressed in enhanced pause (Penh), an index of airway obstruction as described in detail previously. 48 STS mice were not exposed to doses above 12.5 mg/ml methacholine as higher doses induce a very severe bronchoconstrictive reaction.…”

Section: Airway Responsivenessmentioning

confidence: 99%

Mouse genetic model for antigen-induced airway manifestations of asthma

et al. 2006

View full text Add to dashboard Cite

Allergic asthma is a genetically complex disease characterized by allergen-specific immunoglobulin (Ig)E, eosinophilic inflammation of the lungs and airway hyper-responsiveness to bronchospasmogenic stimuli. In this study, we compared 13 recombinant congenic (RC) mouse strains in an ovalbumin model of allergic asthma. Different intensities and types of responses are observed throughout the RC strains. Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain. All strains show a 'modified' Th2 response except CcS14, which shows a 'true' Th2 response. When data from all strains are pooled, airway reactivity shows significant correlations with the serum Ig levels and the levels of interleukin (IL)-4, IL-5 and IL-13 in the broncho-alveolar lavage (BAL), at low dosage of methacholine (below 25 mg/ml), whereas at high dosage airway reactivity only correlates with BAL neutrophil levels. This indicates that at least two different mechanisms are involved in the airway reactivity to methacholine. None of these correlations can be found in every individual strain, which demonstrates that the asthma traits in this mouse model are genetically dissociated and that the loci can be genetically mapped.

show abstract

Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model

Cited by 75 publications

References 26 publications

Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

Mouse genetic model for antigen-induced airway manifestations of asthma

Contact Info

Product

Resources

About