Resolution of Der p1-Induced Allergic Airway Inflammation Is Dependent on CD4+CD25+Foxp3+ Regulatory Cells

Leech, Melanie D.; Benson, Robert A.; Vries, Annick de; Fitch, Paul M.; Howie, Sarah

doi:10.4049/jimmunol.179.10.7050

Cited by 88 publications

(93 citation statements)

References 26 publications

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“…These cells were able to suppress OVA-specific T cell proliferation ex vivo. Other reports have shown that depletion of CD4ϩCD25ϩ cells before acute airway allergen challenges exacerbated lung eosinophilia, and adoptive transfer of these cells can also significantly protect against developing lung inflammation (26,29). Not surprisingly, mice deficient in Foxp3 have increased lung inflammation and smooth muscle mass after repetitive antigen challenge (10).…”

Section: Discussionmentioning

confidence: 99%

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

Doherty¹,

Soroosh²,

Broide³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionmentioning

confidence: 99%

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

Doherty¹,

Soroosh²,

Broide³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Sections were stained with hematoxylin and eosin (H&E) or Periodic acid-Schiff (PAS). Slides were scored for the presence of goblet cells as previously described (55). Average percentages of goblet cells within 10 consecutive small airways (less than half the width of a field at ×200 magnification) were calculated for each slide, under experimentally blinded conditions.…”

Section: Methodsmentioning

confidence: 99%

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mackenzie

Nowakowska

Leech

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergenexperienced T cells. CD62L expression by allergen-experienced T cells corresponds to effector/effector memory (CD62L lo ) and central memory (CD62L hi ) subsets, which vary with allergen exposure (e.g., during, or out with, pollen season). The efficacy of PIT on different T helper 2 (Th2) cell memory populations is unknown. We developed a murine model of PIT in allergic airway inflammation (AAI) driven by adoptively transferred, traceable ovalbumin-experienced Th2 cells. PIT effectively suppressed AAI driven by unfractionated Th2 cells. Selective transfer of CD62L hi and CD62L lo Th2 cells revealed that these two populations behaved differently from one another and from previously characterized (early deletional) responses of naive CD4 + T cells to PIT. Most notably, allergen-reactive CD62L lo Th2 cells were long-lived within the lung after PIT, before allergen challenge, in contrast to CD62L hi Th2 cells. Despite this, PIT was most potent against CD62L lo Th2 cells in protecting from AAI, impairing their ability to produce Th2 cytokines, whereas this capacity was heightened in PIT-treated CD62L hi Th2 cells. We conclude that Th2 cells do not undergo an early deletional form of tolerance after PIT. Moreover, memory Th2 subsets respond differently to PIT. These findings have implications for the clinical translation of PIT in different allergic scenarios.

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“…17,19,20 Anti-nuclear autoantibodies (ANA) were detected by means of indirect immunofluorescence at 1:20 serum as a starting dilution by an observer blinded to the experimental conditions, as described in the Methods section in this article's Online Repository.…”

Section: Induction Of Experimental Allergic Sensitizationmentioning

confidence: 99%

A novel allergen-adjuvant conjugate suitable for specific immunotherapy of respiratory allergy

Filì¹,

Vultaggio²,

Cardilicchia³

et al. 2013

Journal of Allergy and Clinical Immunology

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Background: Several approaches to find a better adjuvant, focus immunomodulation, and reduce allergenicity are under investigation to improve the efficacy and safety of specific immunotherapy. Objective: We performed an investigation of the in vitro and in vivo effects of a purified allergen chemically conjugated to a novel 8-OH modified adenine as an adjuvant. Methods: Purified group 2 major allergen from house dust mite chemically conjugated to 4-(6-amino-9-benzyl-8-hydroxy-9H-purin-2-ylsulfanyl)-butyric acid succinimidyl ester was analyzed by using mass spectrometry. The adduct (nDer p 2-Conj) was assayed for Toll-like receptor activation on transfected HEK293 cells, stimulation of innate cells, and effects on the functional phenotype of specific T-cell lines and clones by means of flow cytometry, real-time PCR, and expression of T H -related transcription factors. Lung cells and sera of nDer p 2-Conjsensitized C57Bl/6 mice were studied by means of cytology, histology, real-time PCR, and ELISA. Results: nDer p 2-Conj stimulated IL-12 and IFN-a production from monocytes and plasmacytoid dendritic cells, respectively, retaining the ability to trigger Toll-like receptor 7 exclusively, and expanded human allergen-specific lymphocytes with reduced ability to produce T H 2-related cytokines and increased IFN-g levels, as based on GATA-3/T-bet expression. In vivo adduct-sensitized mice exhibited reduced eosinophil infiltration and IL-13 expression in the airways, IFN-g upregulation together with IgE downregulation, and an increase in allergenspecific IgG 2a levels in sera. The conjugate exhibited reduced ability to activate human FcεRI 1 cells without inducing T H 17 cells or autoantibodies.

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Resolution of Der p1-Induced Allergic Airway Inflammation Is Dependent on CD4+CD25+Foxp3+ Regulatory Cells

Cited by 88 publications

References 26 publications

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

A novel allergen-adjuvant conjugate suitable for specific immunotherapy of respiratory allergy

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