Transforming growth factor beta 1 plays an important role in inducing CD4(+)CD25(+)forhead box P3(+) regulatory T cells by mast cells.
The role of mast cells (MCs) in the generation of adaptive immune responses especially in the transplant immune responses is far from being resolved. It is reported that mast cells are essential intermediaries in regulatory T cell (T(reg)) transplant tolerance, but the mechanism has not been clarified. To investigate whether bone marrow-derived mast cells (BMMCs) can induce T(regs) by expressing transforming growth factor beta 1 (TGF-β1) in vitro, bone marrow cells obtained from C57BL/6 (H-2(b) ) mice were cultured with interleukin (IL)-3 (10 ng/ml) and stem cell factor (SCF) (10 ng/ml) for 4 weeks. The purity of BMMCs was measured by flow cytometry. The BMMCs were then co-cultured with C57BL/6 T cells at ratios of 1:2, 1:1 and 2:1. Anti-CD3, anti-CD28 and IL-2 were administered into the co-culture system with (experiment groups) or without (control groups) TGF-β1 neutralizing antibody. The percentages of CD4(+)CD25(+)forkhead box P3 (FoxP3)(+) T(regs) in the co-cultured system were analysed by flow cytometry on day 5. The T(reg) percentages were significantly higher in all the experiment groups compared to the control groups. These changes were deduced by applying TGF-β1 neutralizing antibody into the co-culture system. Our results indicated that the CD4(+) T cells can be induced into CD4(+)CD25(+)FoxP3(+) T cells by BMMCs via TGF-β1.
Zhang
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Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Wu
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He
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Gao
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Huang
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W
Lin
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Cai
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L
Fang
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Zhou
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Q
Luo
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Chen
Z K
ZK
Zhou
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H
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D057134:Antibodies, Neutralizing; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1