CD4(+)CD25(+)Foxp3(+)Regulatory T cells (Tregs) play important roles in regulating allergic
inflammation. To analyse if
allergen-
DNA-modified dendritic cells (DC) can suppress allergic responses and what roles Treg cells play in DC-based
allergen-specific
immunotherapy. Immature DC were transfected with retrovirus encoding Der p2
DNA, and administered to mice that sensitized and challenged with Der p2
protein. After Treg cells were depleted with anti-CD25 mAb, mice were re-challenged to observe the airway
inflammation, and Treg cells in spleen CD4(+) T cells. And responses of spleen CD4(+) T cells to Der p2 were determined. Co-culture of naïve CD4(+) T cells with
allergen-modified DC induced Foxp3+ Tregs. Sensitized and challenged mice developed allergic airway
inflammation and Th2 responses, and decreased Foxp3(+) Tregs. Treatment with
allergen-modified-DC suppressed airway
inflammation and Th2 responses, and increased
IL-10 and IFN-gamma production and Foxp3(+) Tregs significantly; and eliminated the responses of CD4(+) T cells to
allergen. Administration of anit-CD25 mAb eliminated all the effects of modified-DC except for the increasing of IFN-gamma.
Allergen-modified DC can induce immune tolerance to
allergens and reverse the established Th2 responses induced by
allergen, with dependence on the induction of Foxp3(+) Tregs.