Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3+ Regulatory T cells.
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.
Wu
Kui
K
Institute of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Bi
Yuttian
Y
Sun
Kun
K
Xia
Junbo
J
Wang
Yan
Y
Wang
Changzheng
C
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006651:Histocytochemistry; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D008168:Lung / Q000166:cytology / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014162:Transfection
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007073:Immunoglobulin E