CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease

Martin, Helen; Reuter, Sebastian; Dehzad, Nina; Heinz, A.; Bellinghausen, Iris; Saloga, Joachim; Haasler, Ina; Korn, Stephanie; Jonuleit, Helmut; Buhl, Roland; Becker, Christian; Taube, Christian

doi:10.1016/j.jaci.2011.09.038

Cited by 30 publications

(41 citation statements)

References 33 publications

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“…22 However, coinjection of sGARP with nonprotective numbers of Treg inhibited GVHD onset by enhancing Treg activity significantly, and repetitive application of sGARP prevented disease onset completely, supporting the idea of sGARP as a potent Treg enhancer and inhibitor of T effector cell induction. Therapeutic application of sGARP in disease models such as allergy, 39 asthma, 40 or rheumatoid arthritis should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells

Hahn

Stahl

Becker

et al. 2013

Blood

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Key Points• GARP efficiently represses proliferation of naïve and resting CD4 1 T cells and is involved in the induction of adaptive regulatory T cells.• In vivo, GARP prevents T cell-mediated destructive inflammation in a preclinical humanized mouse model of GVHD.Glycoprotein A repetitions predominant (GARP) is expressed on the surface of activated human regulatory T cells (Treg) and regulates the bioavailability of transforming growth factor-b (TGF-b). GARP has been assumed to require membrane anchoring. To investigate the function of GARP in more detail, we generated a soluble GARP protein (sGARP) and analyzed its impact on differentiation and activation of human CD4 1 T cells.We demonstrate that sGARP efficiently represses proliferation and differentiation of naïve

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Section: Discussionmentioning

confidence: 99%

Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells

Hahn

Stahl

Becker

et al. 2013

Blood

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“…Periodic acid-Schiff staining was performed to visualize mucusproducing goblet cells, as described before (34). Collagen deposition in chronic airway inflammation was assessed on Sirius red-stained sections.…”

Section: Pathologymentioning

confidence: 99%

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

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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.

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“…Because of the high differences in the frequencies and levels of PBMC engraftment depending on donor and recipient variability, it is difficult to use these mice for analysis of novel inhibitory strategies for the treatment of allergic diseases. Here we describe for the first time a reliable and reproducible model of allergic inflammation in NOD-scid-gc 2/2 mice engrafted with PBMCs from allergic donors together with the respective allergen, resulting in proliferation, cytokine production, allergen-specific IgE production, and allergen-induced inflammation in the colon and airways/lung (the latter published separately 25 ). The presented model might be useful to study novel immunotherapeutic drugs or strategies for the treatment of allergic diseases, including food allergy.…”

Section: Discussionmentioning

confidence: 99%

Allergen-induced IgE-dependent gut inflammation in a human PBMC–engrafted murine model of allergy

Weigmann

Schughart

Wiebe

et al. 2012

Journal of Allergy and Clinical Immunology

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CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease

Cited by 30 publications

References 33 publications

Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells

Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells

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

Allergen-induced IgE-dependent gut inflammation in a human PBMC–engrafted murine model of allergy

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