6533b872fe1ef96bd12d3956

RESEARCH PRODUCT

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

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Abstract Background Atopic-allergic diseases are characterized by T H 2-dominated immune responses, resulting in IgE production. DNA-based immunotherapies have been shown to shift the immune response toward a T H 1-type response in animal models. Objective 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 H 1 cytokines instead of T H 2 cytokines. Methods 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. Results 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 H 1 immune response compared with T cells stimulated with allergen-pulsed DCs. Conclusions 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 H 2 dominance toward T H 1 dominance.