The Journal of Allergy and Clinical Immunology
Volume 125, Issue 4 , Pages 896-901.e6, April 2010

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

  • John T. Schroeder, PhD

      Affiliations

    • Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • Corresponding Author InformationReprint requests: John T. Schroeder, PhD, Unit Office 2, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.
    • ,
  • Anja P. Bieneman, BS

      Affiliations

    • Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • ,
  • Kristin L. Chichester, MS

      Affiliations

    • Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • ,
  • Robert G. Hamilton, PhD

      Affiliations

    • Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • ,
  • HuiQing Xiao, MD

      Affiliations

    • Division of Pulmonary and Critical Care Medicine at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • ,
  • Sarbjit S. Saini, MD

      Affiliations

    • Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • ,
  • Mark C. Liu, MD

      Affiliations

    • Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md
    • Division of Pulmonary and Critical Care Medicine at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md

Received 14 May 2009; received in revised form 13 October 2009; accepted 20 October 2009. published online 05 February 2010.

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, FcεRIα, 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 FcεRIα 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.

Key words: Dendritic cells, IgE, antigen presentation, cytokine, receptor

Abbreviations used: APC, Antigen-presenting cell, BAU, Bioequivalent allergy unit, BDC, Basophil-depleted cell, BDCA, Blood dendritic cell antigen, DC, Dendritic cell, IQR, Interquartile range, mDC, Myeloid dendritic cell, nMFI, Net median fluorescence intensity, pDC, Plasmacytoid dendritic cell

 

 Supported by the Asthma and Allergic Diseases Cooperative Research Centers grant U19AI070345-01 (project 3; J.T.S.) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

 Disclosure of potential conflict of interest: J. T. Schroeder has received research support from Sanofi-Aventis, Schering-Plough, and Inotek. S. S. Saini is a consultant for and has received research support from Genentech/Novartis. M. C. Liu is a speaker for GlaxoSmithKline, AstraZeneca, and Sepracor; is on the Ad Board for Merck, Amgen, and Centocor; is on the Data Safety Monitoring Board for Ception; has received research support from Amgen, Pfizer, and Centocor; and is a Board Member of the American Lung Association of the Atlantic Coast. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)01549-8

doi:10.1016/j.jaci.2009.10.021

The Journal of Allergy and Clinical Immunology
Volume 125, Issue 4 , Pages 896-901.e6, April 2010

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