Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response.
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-4(low)] and Der p 1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T cell polarization (IFN-gamma(low)/IL-4(low)) 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.
Charbonnier
Anne-Sophie
AS
Unité INSERM U416, IFR 17, Institut Pasteur de Lille, 1 rue du Professeur Calmette, B.P. 245, 59019 Lille Cedex, France. anne-sophie.charbonnier@pasteur-lille.fr
Hammad
Hamida
H
Gosset
Philippe
P
Stewart
Geoffrey A
GA
Alkan
Sefik
S
Tonnel
André-Bernard
AB
Pestel
Joël
J
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000494:pharmacology; D060829:Arthropod Proteins; D001773:Blood Cells; D016022:Case-Control Studies; D018920:Coculture Techniques; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D022423:Myeloid Cells; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D006684:HLA-DR Antigens; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1