title: The suppressive effect of CD25+Treg cells on Th1 differentiation requires cell-cell contact partially via TGF-β production.
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 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.
authors.affiliation: Department of Immunology, State Ministry of Education-Key Laboratory of Tropical Diseases Control Research, Zhongshan School of Medicine, Sun Yatsen University, Guangzhou, Guangdong, Peoples Republic of China.
authors.forename: Erxia
authors.initials: E
authors.lastname: Shen
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D001973:Bromodeoxyuridine / Q000032:analysis; D002450:Cell Communication; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005452:Fluoresceins / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017634:Self Tolerance / Q000276:immunology*; D013388:Succinimides / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058408:Th1-Th2 Balance; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D057134:Antibodies, Neutralizing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001973:Bromodeoxyuridine; D005452:Fluoresceins; D007371:Interferon-gamma; D016753:Interleukin-10; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D013388:Succinimides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester