Allergen-specific immune deviation from a TH2 to a TH1 response induced by dendritic cells and collagen type I.
BACKGROUND
Atopy and IgE production are associated with enhanced allergen-specific T(H)2 responses. Therefore a causative treatment may result from the deviation of this T(H)2-dominated immune response toward a T(H)1 response.


OBJECTIVE
This study was carried out to analyze whether dendritic cells, the most potent antigen-presenting cells that are also known to induce antigen-specific T(H)1 responses, are suitable for therapy of atopic diseases by shifting the allergen-specific T(H)2 response toward a T(H)1 response.


METHODS
Monocyte-derived dendritic cells were used to present allergens in vitro to autologous CD4(+) T cells of allergic persons. Because collagen type I activates dendritic cells and enhances the secretion of IL-12, we performed allergen presentation assays also in the presence of collagen type I.


RESULTS
After stimulation with allergen-pulsed dendritic cells the production of IFN-gamma as well as that of IL-4 and IL-5 by CD4(+) T cells was enhanced. In the presence of collagen type I, however, a significant shift toward a T(H)1 response with increased production of IFN-gamma and a decreased production of IL-5 could be observed. When T cells were stimulated directly with anti-CD3 and anti-CD28 in the absence of antigen-presenting cells, it was demonstrated that collagen type I also exerted a direct effect on T cells, increasing their IFN-gamma production.


CONCLUSIONS
These data indicate that collagen type I influences dendritic cells as well as T cells in a way that a shift in cytokine production results in a T(H)1 response even in already-sensitized atopic individuals.
Brand
U
U
Clinical Research Unit, Department of Dermatology, University of Mainz, Mainz, Germany.
Bellinghausen
I
I
Enk
A H
AH
Jonuleit
H
H
Becker
D
D
Knop
J
J
Saloga
J
J
D000485:Allergens / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen