A CD1d-Dependent Antagonist Inhibits the Activation of Invariant NKT Cells and Prevents Development of Allergen-Induced Airway Hyperreactivity

Lombardi, Vincent; Stock, Philippe; Singh, Ashish Kumar; Kerzerho, Jérôme; Yang, Wen; Sullivan, Barbara A.; Li, Xiangming; Shiratsuchi, Takayuki; Hnatiuk, Nathan E.; Howell, Amy R.; Yu, Karl O. A.; Porcelli, Steven A.; Tsuji, Moriya; Kronenberg, Mitchell; Wilson, S. Brian; Akbari, Omid

doi:10.4049/jimmunol.0901208

Cited by 42 publications

(31 citation statements)

References 54 publications

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“…On the other hand, neither OVA-induced airway inflammation nor AHR were inducible in iNKT cell-deficient mice, indicating an important causative role for these cells [334]. These observations were supported by experiments applying anti-CD1d antibodies to animals and by treatment with CD1d-dependent antagonists, both suppressing OVA-induced AHR and inflammation [333,342]. Of note, Akbari et al [343] demonstrated that more than half of the pulmonary CD4 + cells in human bronchial asthma belong to the iNKT lineage.…”

Section: Contribution Of Nk T Cells To Allergic Immune Responsessupporting

confidence: 59%

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Neunkirchner

Schmetterer

Pickl

2014

Int Arch Allergy Immunol

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During the last decades, a multitude of studies applying distinct in vitro and in vivo model systems have contributed greatly to our better understanding of the initiation and regulation of inflammatory processes leading to allergic diseases. Over the years, it has become evident that among lymphocytes, not only IgE-producing B cells and allergy-orchestrating CD4⁺ helper cells but also cytotoxic CD8⁺ T cells, γδ-T cells and innate lymphoid cells, as well as regulatory lymphocytes, might critically shape the immune response towards usually innocuous allergens. In this review, we provide a historic overview of pioneering work leading to the establishment of important lymphocyte-based model systems for allergy research. Moreover, we contrast the original findings with our currently more refined knowledge to appreciate the actual validity of the respective models and to reassess the conclusions obtained from them. Conflicting studies and interpretations are identified and discussed. The tables are intended to provide an easy overview of the field not only for scientists newly entering the field but also for the broader readership interested in updating their knowledge. Along those lines, herein we discuss in vitro and in vivo approaches to the investigation of lymphocyte effector cell activation, polarization and regulation, and describe depletion and adoptive transfer models along with gene knockout and transgenic (tg) methodologies. In addition, novel attempts to establish humanized T cell antigen receptor tg mouse models for allergy research are described and discussed.

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Section: Contribution Of Nk T Cells To Allergic Immune Responsessupporting

confidence: 59%

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Neunkirchner

Schmetterer

Pickl

2014

Int Arch Allergy Immunol

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“…Recently, a CD1d-dependent antagonist, dipalmitoyl phosphatidylethanolamine polyethylene glycol, has been shown to inhibit NKT cells and suppress AHR (55). However, dipalmitoyl phosphatidylethanolamine polyethylene glycol had no effect on the development of OVA-specific Th2 responses.…”

Section: Discussionmentioning

confidence: 97%

Components of Streptococcus pneumoniae Suppress Allergic Airways Disease and NKT Cells by Inducing Regulatory T Cells

Thorburn

Foster

Gibson

et al. 2012

The Journal of Immunology

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Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.

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“…A CD1d-binding lipid antagonist prevented AHR in a murine model of allergen challenge but had no effect on T H 2 cells. 81 Interestingly, CD1d-restricted NKT cell clones recognized phospholipids from cypress pollens, although more phospholipid-responsive clones were conventional CD4 1 T cells or gd T cells. 82 gd T cells use a T-cell receptor comprising g and d chains as opposed to the classical ab T-cell receptor found on most CD4 1 T cells.…”

Section: Other T Cells: Cd8 T Cells Nkt Cells and Gd T Cellsmentioning

confidence: 98%