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

Abstract

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. 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. 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(H)1 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(H)2 dominance toward T(H)1 dominance.