Modification of the human allergic immune response by allergen-DNA-transfected dendritic cells in vitro.
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.
Klostermann
Bettina
B
Department of Dermatology, University of Mainz, Mainz, Germany.
Bellinghausen
Iris
I
Böttcher
Ingo
I
Petersen
Arnd
A
Becker
Wolf-Meinhard
WM
Knop
Jürgen
J
Saloga
Joachim
J
D000260:Adenoviruses, Human / Q000235:genetics*; D000485:Allergens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection
D000485:Allergens; D016207:Cytokines; D010940:Plant Proteins; C090396:PHLPI protein, Phleum pratense; D007371:Interferon-gamma