The suppressive effect of CD25+Treg cells on Th1 differentiation requires cell—cell contact partially via TGF-β production

Authors

  • Erxia Shen,

    1. Department of Immunology, State Ministry of Education Key Laboratory of Tropical Diseases Control Research, Zhongshan School of Medicine, Sun Yatsen University, Guangzhou, Guangdong 510080, Peoples Republic of China
    2. Department of Microbiology and Immunology, School of Basic Medicine, Guangzhou Medical University, Guangzhou, Guangdong, 510182, Peoples Republic of China
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  • Kai Zhao,

    1. Department of Immunology, State Ministry of Education Key Laboratory of Tropical Diseases Control Research, Zhongshan School of Medicine, Sun Yatsen University, Guangzhou, Guangdong 510080, Peoples Republic of China
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  • Changyou Wu,

    1. Department of Immunology, State Ministry of Education Key Laboratory of Tropical Diseases Control Research, Zhongshan School of Medicine, Sun Yatsen University, Guangzhou, Guangdong 510080, Peoples Republic of China
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  • Binyan Yang

    Corresponding author
    1. Department of Immunology, State Ministry of Education Key Laboratory of Tropical Diseases Control Research, Zhongshan School of Medicine, Sun Yatsen University, Guangzhou, Guangdong 510080, Peoples Republic of China
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To whom correspondence should be addressed (email binyan_yang@yahoo.com).

Abstract

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)-γ and the percentage of IFN-γ-, IL-2 and TNF-α-producing cells by CD25T cells under Th1 cell culture conditions and suppress the differentiation of CD25T cells into Th1 cells in a dose-dependent manner. Moreover, these CD25+Treg cells could inhibit the activation of CD25T cells by down-regulating the expression of activation markers CD69 and CD25 and suppress the division and proliferation of CD25T 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-β 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-β. This finding strongly indicates a therapeutic role for CD25+Treg cells in Th1-mediated diseases.

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