title: Activation of natural killer T cells inhibits the development of induced regulatory T cells via IFNγ.
abstract: Recent reports have provided evidence for cross-talk between regulatory T (Treg) cells and natural killer T (NKT) cells. However, it is unclear whether NKT cells play a role in the differentiation of Treg cells. By employing NKT cell-abundant Vα14 TCR transgenic (Tg) and NKT cell-deficient CD1d knock-out (KO) mice, we examined the effects of NKT cells on the in vitro differentiation of induced Treg (iTreg) cells with IL2 and TGFβ. We found that iTreg induction from CD1d KO mice was significantly increased compared to the control. Also, the addition of isolated NKT cells from Vα14 TCR Tg mice to naïve CD4(+) T cells from CD1d KO mice during iTreg differentiation caused a remarkable reduction of iTreg cells. Through IFNγ neutralization, we showed that this reduction was mediated by IFNγ. Furthermore, the main source of IFNγ during iTreg differentiation was NK1.1(-)CD4(+)Foxp3(-) T cells. This finding implied that early-activated NKT cells induced Th1-type cells and subsequently underwent apoptosis. Taken together, our results suggest that NKT cells inhibit the in vitro development of iTreg cells by increasing IFNγ.
authors.affiliation: Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Kyu Heon
authors.initials: KH
authors.lastname: Oh
authors.forename: Changjin
authors.initials: C
authors.lastname: Lee
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Sung H
authors.initials: SH
authors.lastname: Jeon
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Rho H
authors.initials: RH
authors.lastname: Seong
authors.forename: Seokmann
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma