Induction of CD4+CD25+Foxp3+IL-10+ T cells in HDM-allergic asthmatic children with or without SIT.
BACKGROUND
Regulatory T cells and immunosuppressive cytokines, such as IL-10 and TGF-beta(1), may have a role in clinically effective allergen-specific immunotherapy. IL-10-secreting regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the frequency and function of regulatory T cells in the response to house dust mite (HDM) immunotherapy.


METHODS
PBMCs were isolated from 27 HDM-allergic asthmatic children who underwent immunotherapy for 1.5-2 years (SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 h of in vitro stimulation with HDM extracts, regulatory T cells were measured by flow cytometry. Production of IL-4, IFN-gamma and TGF-beta(1 )in supernatants from allergen-stimulated cultures and the PBMC proliferations were measured by ELISA. Sera were tested for allergen-specific IgE using the ImmunoCAP 100 assay.


RESULTS
Patients undergoing immunotherapy produced significantly more IL-10 and showed a significant reduction in proliferation induced by HDM extract compared with the asthma group. In cultures stimulated with HDM extract, the amounts of IL-4 and TGF-beta were lower and the amounts of IFN-gamma were higher in the SIT group compared with the asthma group.


CONCLUSIONS
There is a functional, but quantitative, insufficiency of Treg cells in allergic asthmatic children, which was reversed in SIT-treated children. SIT can up-regulate the function of CD4(+)CD25(+)Foxp3(+) Treg cells.
Wei
Wang
W
Asthma Center, Beijing Children's Hospital, Capital Medical University, 56 South Lishi Road, Beijing, PR China.
Liu
Yongge
Y
Wang
Yonghong
Y
Zhao
Yuhong
Y
He
Jianxin
J
Li
Xiang
X
Shen
Kunling
K
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000628:therapy; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D039981:Pyroglyphidae / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015854:Up-Regulation
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10