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

• Published in: Cell biology international Vol. 35; no. 7; pp. 705 - 712
• Main Authors: Shen, Erxia, Zhao, Kai, Wu, Changyou, Yang, Binyan
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2011
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - biosynthesis; Antigens, Differentiation, T-Lymphocyte - immunology; Bromodeoxyuridine - analysis; Cell Communication; Cell Differentiation - immunology; differentiation; Female; Fluoresceins - analysis; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Interleukin-2 Receptor alpha Subunit - biosynthesis; Interleukin-2 Receptor alpha Subunit - immunology; Lectins, C-Type - biosynthesis; Lectins, C-Type - immunology; Mice; Mice, Inbred BALB C; Self Tolerance - immunology; Succinimides - analysis; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Th1; Th1 Cells - cytology; Th1 Cells - immunology; Th1-Th2 Balance; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - immunology; Treg cell; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1042/CBI20100528

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 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 CD69 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‐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.