Modification of the human allergic immune response by allergen-DNA–transfected dendritic cells in vitro

• Published in: Journal of allergy and clinical immunology 2004-02, Vol.113 (2), p.327-333
• Main Authors: Klostermann, Bettina, Bellinghausen, Iris, Böttcher, Ingo, Petersen, Arnd, Becker, Wolf-Meinhard, Knop, Jürgen, Saloga, Joachim
• Format: Article
• Language: English
• Subjects: Adenoviral transfection; Adenoviruses; Adenoviruses, Human - genetics; Allergens - genetics; Allergens - immunology; Allergies; allergy; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cytokines - metabolism; dendritic cells; Dendritic Cells - immunology; Deoxyribonucleic acid; DNA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Vectors; Humans; Hypersensitivity, Immediate - immunology; Immune system; Immunopathology; Interferon-gamma - biosynthesis; Lymphocyte Activation; Lymphocytes; Medical research; Medical sciences; Plant Proteins - genetics; Plant Proteins - immunology; Plasma; Proteins; T H1/T H2; Th1 Cells - immunology; Transfection
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2003.10.067

Atopic-allergic diseases are characterized by T H2-dominated immune responses, resulting in IgE production. DNA-based immunotherapies have been shown to shift the immune response toward a T H1-type response in animal models. The aim of the study was to analyze whether dendritic cells (DCs) transfected with allergen-DNA conjugates are able to stimulate human autologous CD4 + T cells, CD8 + T cells, or both from atopic individuals to produce T H1 cytokines instead of T H2 cytokines. For this purpose, human mature DCs from atopic donors were transfected with an adenovirus encoding the allergen Phl p 1. Autologous CD4 + and CD8 + T cells were stimulated with these transfected DCs, and proliferation and cytokine production were measured. By using an adenoviral vector, a transfection rate of 92% could be achieved. The proliferative response of CD4 + T cells stimulated with autologous transfected DCs was concentration dependent and almost as high as that of T cells stimulated with mature allergen-pulsed DCs. The proliferation of CD8 + T cells stimulated with transfected DCs, however, was higher than that of cells stimulated with allergen-pulsed DCs. The cytokine pattern showed a shift toward a T H1 immune response compared with T cells stimulated with allergen-pulsed DCs. Human DCs can be transfected with allergen-DNA conjugates very efficiently by using an adenoviral vector yielding DCs with high T-cell stimulatory capacities, directing the atopic-allergic immune response from T H2 dominance toward T H1 dominance.