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(Journal of Leukocyte Biology. 2003;73:91-99.)
© 2003 by Society for Leukocyte Biology

Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response

Anne-Sophie Charbonnier*, Hamida Hammad{dagger}, Philippe Gosset*, Geoffrey A. Stewart{ddagger}, Sefik Alkan§, André-Bernard Tonnel* and Joël Pestel*

* Unité INSERM U416, IFR 17, Institut Pasteur de Lille, Cedex, France;
{dagger} Erasmus University of Rotterdam, The Netherlands;
{ddagger} Department of Microbiology, University of Western Australia, Nedlands, Perth;
§ Aventis Pharmaceuticals, Bridgewater, New Jersey; and
Department of Pneumology, Hôpital A. Calmette, CHRU de Lille, Cedex, France

Correspondence: Anne-Sophie Charbonnier, Unité INSERM U416, Institut Pasteur de Lille, 1 rue du Professeur Calmette, B.P. 245, 59019 Lille Cedex, France. E-mail: anne-sophie.charbonnier{at}pasteur-lille.fr

Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4+ T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-{gamma}high/IL-4low] and Der p 1-pulsed P-DC, a Th2 profile (IFN-{gamma}low/IL-4high). In healthy donors, no T cell polarization (IFN-{gamma}low/IL-4low) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.

Key Words: allergy • steady state • Th1/Th2 response




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