Journal
CELL BIOLOGY INTERNATIONAL
Volume 35, Issue 7, Pages 705-712Publisher
WILEY
DOI: 10.1042/CBI20100528
Keywords
differentiation; Th1; Treg cell
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Funding
- National Natural Science Foundation of China [30872310]
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CD25(+)Treg cells (CD4(+)CD25(+)Foxp3(+) regulatory T cells) play a central role in the maintenance of peripheral self-tolerance and immune homoeostasis. A previous study showed that CD25(+)Treg cells suppressed the differentiation and function of Th1 cells in vivo and in vitro. However, the mechanism of suppressing Th1 cell differentiation mediated by CD25(+)Treg cells remains unclear. In the present study, we found that CD25(+)Treg cells could reduce the production of IFN (interferon)-gamma and the percentage of IFN-gamma-, IL-2 and TNF-alpha-producing cells by CD25(-)T cells under Th1 cell culture conditions and suppress the differentiation of CD25(-)T cells into Th1 cells in a dose-dependent manner. Moreover, these CD25(+)Treg cells could inhibit the activation of CD25(-)T cells by down-regulating the expression of activation markers 0069 and CD25 and suppress the division and proliferation of CD25(-)T cells using CFSE (carboxyfluorescein diacetate succinimidyl ester)-labelling and BrdU (5-bromo-20-deoxyuridine) incorporation, respectively. Further studies showed that the suppressive effects of CD25(+)Treg cells on Th1 cell differentiation required cell-cell contact and was partially restored by the addition of anti-TGF-beta mAb (monoclonal antibody) but not anti-IL-10 mAb, indicating that the suppression mechanism of CD25(+)Treg cells was cell-cell contact dependent and partially via TGF-beta. This finding strongly indicates a therapeutic role for CD25(+)Treg cells in Th1-mediated diseases.
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