Decreases in human dendritic cell-dependent T(H)2-like responses after acute in vivo IgE neutralization.
BACKGROUND
Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as alphagamma(2), which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to T(H) cells.


OBJECTIVE
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, FcepsilonRIalpha, 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 > or =95% posttreatment (P = .0005), whereas FcepsilonRIalpha expression decreased by 66% and 48%, respectively (P = .0005). Cat allergen-induced proliferation in DC/T-cell cocultures observed at baseline was suppressed approximately 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-gamma were unaltered or slightly increased. These changes were not evident in placebo-control subjects (n = 4).


CONCLUSIONS
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.
Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md, USA. schray@jhmi.edu
John T
JT
Schroeder
Anja P
AP
Bieneman
Kristin L
KL
Chichester
Robert G
RG
Hamilton
Huiqing
H
Xiao
Sarbjit S
SS
Saini
Mark C
MC
Liu
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology*; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002415:Cats; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004311:Double-Blind Method; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D000069444:Omalizumab; D017455:Receptors, IgE / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D016207:Cytokines; D017455:Receptors, IgE; D000069444:Omalizumab; D007073:Immunoglobulin E