Decreases in human dendritic cell-dependent TH2-like responses after acute in vivo IgE neutralization

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Abstract

Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as αγ2, which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to TH cells. Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo. Methods: Subjects with cat allergy were enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid and myeloid DCs were assessed at baseline and posttreatment for expression of surface IgE, Fcε{lunate}RIα, and induction of CD4+T-cell proliferation and cytokine responses to cat allergen. Results: IgE expression on plasmacytoid and myeloid DCs from omalizumab-treated subjects (n = 12) decreased by ≥95% posttreatment (P = .0005), whereas Fcε{lunate}RIα expression decreased by 66% and 48%, respectively (P = .0005). Cat allergen-induced proliferation in DC/T-cell cocultures observed at baseline was suppressed ∼20% to 40% postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P <.05), whereas IL-2 and IFN-γ were unaltered or slightly increased. These changes were not evident in placebo-control subjects (n = 4). Conclusion: IgE likely facilitates allergen presentation by dendritic cells in vivo and is also important in regulating DC-dependent T-cell cytokines during effector phases of allergic disease.

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume125
Issue number4
DOIs
StatePublished - Apr 2010

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Dendritic Cells
Immunoglobulin E
Allergens
T-Lymphocytes
Cats
Myeloid Cells
Cytokines
Coculture Techniques
Placebos
IgE Receptors
Interleukin-13
Interleukin-5
Antigen-Presenting Cells
Interleukin-10
Interleukin-2
Hypersensitivity
Asthma
Cell Proliferation
Omalizumab

Keywords

  • antigen presentation
  • cytokine
  • Dendritic cells
  • IgE
  • receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{398597d1961f448e94f2c7dbb8227f9c,
title = "Decreases in human dendritic cell-dependent TH2-like responses after acute in vivo IgE neutralization",
abstract = "Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as αγ2, which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to TH cells. Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo. Methods: Subjects with cat allergy were enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid and myeloid DCs were assessed at baseline and posttreatment for expression of surface IgE, Fcε{lunate}RIα, and induction of CD4+T-cell proliferation and cytokine responses to cat allergen. Results: IgE expression on plasmacytoid and myeloid DCs from omalizumab-treated subjects (n = 12) decreased by ≥95{\%} posttreatment (P = .0005), whereas Fcε{lunate}RIα expression decreased by 66{\%} and 48{\%}, respectively (P = .0005). Cat allergen-induced proliferation in DC/T-cell cocultures observed at baseline was suppressed ∼20{\%} to 40{\%} postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P <.05), whereas IL-2 and IFN-γ were unaltered or slightly increased. These changes were not evident in placebo-control subjects (n = 4). Conclusion: IgE likely facilitates allergen presentation by dendritic cells in vivo and is also important in regulating DC-dependent T-cell cytokines during effector phases of allergic disease.",
keywords = "antigen presentation, cytokine, Dendritic cells, IgE, receptor",
author = "Schroeder, {John Thomas} and Bieneman, {Anja P.} and Chichester, {Kristin L.} and Hamilton, {Robert G} and Huiqing Xiao and Saini, {Sarbjit S} and Liu, {Mark Chang Hwa}",
year = "2010",
month = "4",
doi = "10.1016/j.jaci.2009.10.021",
language = "English (US)",
volume = "125",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Decreases in human dendritic cell-dependent TH2-like responses after acute in vivo IgE neutralization

AU - Schroeder, John Thomas

AU - Bieneman, Anja P.

AU - Chichester, Kristin L.

AU - Hamilton, Robert G

AU - Xiao, Huiqing

AU - Saini, Sarbjit S

AU - Liu, Mark Chang Hwa

PY - 2010/4

Y1 - 2010/4

N2 - Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as αγ2, which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to TH cells. Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo. Methods: Subjects with cat allergy were enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid and myeloid DCs were assessed at baseline and posttreatment for expression of surface IgE, Fcε{lunate}RIα, and induction of CD4+T-cell proliferation and cytokine responses to cat allergen. Results: IgE expression on plasmacytoid and myeloid DCs from omalizumab-treated subjects (n = 12) decreased by ≥95% posttreatment (P = .0005), whereas Fcε{lunate}RIα expression decreased by 66% and 48%, respectively (P = .0005). Cat allergen-induced proliferation in DC/T-cell cocultures observed at baseline was suppressed ∼20% to 40% postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P <.05), whereas IL-2 and IFN-γ were unaltered or slightly increased. These changes were not evident in placebo-control subjects (n = 4). Conclusion: IgE likely facilitates allergen presentation by dendritic cells in vivo and is also important in regulating DC-dependent T-cell cytokines during effector phases of allergic disease.

AB - Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as αγ2, which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to TH cells. Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo. Methods: Subjects with cat allergy were enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid and myeloid DCs were assessed at baseline and posttreatment for expression of surface IgE, Fcε{lunate}RIα, and induction of CD4+T-cell proliferation and cytokine responses to cat allergen. Results: IgE expression on plasmacytoid and myeloid DCs from omalizumab-treated subjects (n = 12) decreased by ≥95% posttreatment (P = .0005), whereas Fcε{lunate}RIα expression decreased by 66% and 48%, respectively (P = .0005). Cat allergen-induced proliferation in DC/T-cell cocultures observed at baseline was suppressed ∼20% to 40% postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P <.05), whereas IL-2 and IFN-γ were unaltered or slightly increased. These changes were not evident in placebo-control subjects (n = 4). Conclusion: IgE likely facilitates allergen presentation by dendritic cells in vivo and is also important in regulating DC-dependent T-cell cytokines during effector phases of allergic disease.

KW - antigen presentation

KW - cytokine

KW - Dendritic cells

KW - IgE

KW - receptor

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U2 - 10.1016/j.jaci.2009.10.021

DO - 10.1016/j.jaci.2009.10.021

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