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RESEARCH PRODUCT

Allergen-specific immune deviation from a T H2 to a T H1 response induced by dendritic cells and collagen type I

Alexander EnkUdo BrandIris BellinghausenDetlef BeckerJoachim SalogaJürgen KnopHelmut Jonuleit

subject

Hypersensitivity ImmediateT-LymphocytesImmunologyAntigen presentationBiologyLymphocyte ActivationInterferon-gammaInterleukin 21Th2 CellsNeutralization TestsHumansImmunology and AllergyCytotoxic T cellIL-2 receptorAntigen-presenting cellCells CulturedAntigen PresentationDendritic CellsDendritic cellAllergensTh1 CellsNatural killer T cellImmunologyInterleukin 12CytokinesCollagenInterleukin-4Interleukin-5

description

Background: Atopy and IgE production are associated with enhanced allergen-specific TH2 responses. Therefore a causative treatment may result from the deviation of this T H2dominated immune response toward a TH1 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 H1 responses, are suitable for therapy of atopic diseases by shifting the allergen-specific TH2 response toward a TH1 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-γ 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 H1 response with increased production of IFN-γ 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- γ production. Conclusion: 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 H1 response even in alreadysensitized atopic individuals. (J Allergy Clin Immunol 1999;104:1052-9.)

https://doi.org/10.1016/s0091-6749(99)70088-6