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The Journal of Immunology, 2002, 169: 1524-1534.
Copyright © 2002 by The American Association of Immunologists

Monocyte-Derived Dendritic Cells Induce a House Dust Mite-Specific Th2 Allergic Inflammation in the Lung of Humanized SCID Mice: Involvement of CCR7

Hamida Hammad1,*, Bart N. Lambrecht1,{dagger}, Pierre Pochard*, Philippe Gosset*, Philippe Marquillies*, André-Bernard Tonnel*,{ddagger} and Joël Pestel2,*

* Institut National de la Santé et de la Recherche Médicale, Unité 416, Institut Pasteur de Lille, Lille, France; {dagger} Department of Pulmonary and Critical Care Medicine, Erasmus University, Rotterdam, The Netherlands; and {ddagger} Clinique des Maladies Respiratoires, Hôpital Calmette, Centre Hospitalier Régional Universitaire de Lille, Lille, France

In rodents, airway dendritic cells (DCs) capture inhaled Ag, undergo maturation, and migrate to the draining mediastinal lymph nodes (MLN) to initiate the Ag-specific T cell response. However, the role of human DCs in the pathogenesis of the Th2 cell-mediated disease asthma remains to be clarified. Here, by using SCID mice engrafted with T cells from either house dust mite (HDM)-allergic patients or healthy donors, we show that DCs pulsed with Der p 1, one of the major allergens of HDM, and injected intratracheally into naive animals migrated into the MLN. In the MLN, Der p 1-pulsed DCs from allergic patients induced the proliferation of IL-4-producing CD4+ T cells, whereas those from healthy donors induced IFN-{gamma}-secreting cells. In reconstituted human PBMC-reconstituted SCID mice primed with pulsed DCs from allergic patients, repeated exposure to aerosols of HDM induced 1) a strong pulmonary inflammatory reaction rich in T cells and eosinophils, 2) an increase in IL-4 and IL-5 production in the lung lavage fluid, and 3) increased IgE production compared with that in mice primed with unpulsed DCs. All these effects were reduced following in vivo neutralization of the CCR7 ligand secondary lymphoid tissue chemokine. These data in human PBMC-reconstituted SCID mice show that monocyte-derived DCs might play a key role in the pathogenesis of the pulmonary allergic response by inducing Th2 effector function following migration to the MLN.




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