title: Th2 polarization by Der p 1--pulsed monocyte-derived dendritic cells is due to the allergic status of the donors.
abstract: The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC--T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite--sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor--alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1--pulsed DCs preferentially produced IL-4 rather than interferon-gamma. These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite--sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure. (Blood. 2001;98:1135-1141)
authors.affiliation: Unité INSERM U416, IFR 17, Institut Pasteur de Lille, France.
authors.forename: H
authors.initials: H
authors.lastname: Hammad
authors.forename: A S
authors.initials: AS
authors.lastname: Charbonnier
authors.forename: C
authors.initials: C
authors.lastname: Duez
authors.forename: A
authors.initials: A
authors.lastname: Jacquet
authors.forename: G A
authors.initials: GA
authors.lastname: Stewart
authors.forename: A B
authors.initials: AB
authors.lastname: Tonnel
authors.forename: J
authors.initials: J
authors.lastname: Pestel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects; D039741:Antigens, Dermatophagoides; D018122:B7-1 Antigen / Q000187:drug effects; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000097:blood*; D007136:Immunoglobulins / Q000187:drug effects; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000187:drug effects; D008925:Mites / Q000276:immunology; D009000:Monocytes / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D006023:Glycoproteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C497964:CD86 protein, human