Allergen-specific immune deviation from a T(H)2 to a T(H)1 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 t he deviation of this T(H)2-dominated immune response toward a T(H)1 respons e. Objective: This study was carried out to analyze whether dendritic cells, t he most potent antigen-presenting cells that are also known to induce antig en-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 t ype I activates dendritic tells and enhances the secretion of IL-12, we per formed allergen presentation assays also in the presence of collagen type I . Results: After stimulation with allergen-pulsed dendritic cells the product ion of IFN-gamma as well as that of IL-4 and IL-5 by CD4(+) T cells was enh anced. In the presence of collagen type I, however, a significant shirt tow ard 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 directl y with anti-CD3 and anti-CD28 in the absence of antigen-presenting cells, i t was demonstrated that collagen type I also exerted a direct effect on T c ells, increasing their IFN-gamma production. Conclusion: These data indicate that collagen type I influences dendritic c ells as well as T cells in a way that a shift in cytokine production result s in a T(H)1 response even in already-sensitized atopic individuals.