title: TGF-β and IL-21 cooperatively stimulate activated CD8(+) T cells to differentiate into Tc17 cells.
abstract: TGF-β together with IL-21 or IL-6 can drive the differentiation of naïve CD8(+) T cells into IL-17-producing CD8(+) T cells. These IL-17-producing CD8(+) T cells are termed Tc17 cells. Tc17 cells preserve plasticity under various conditions in vitro and in vivo. IFN-γ-producing CD8(+) T cells are termed Tc1 cells. However, Tc1 cells are considered relatively stable. In the present study, we show that the combination of TGF-β plus IL-21, but not IL-6, converts Tc1 cells into Tc17 cells; this conversion is associated with elevated RORα, RORγt, and Batf mRNA levels. These results indicate that Tc1 cells are skewed to the Tc17 cell phenotype under TGF-β plus IL-21-polarizing conditions. Furthermore, IL-6R is expressed on naïve, but not activated, CD8(+) T cells. In contrast, IL-21R is expressed on both naïve and activated CD8(+) T cells. Thus, differential expression profiles of IL-6R and IL-21R on naïve and activated CD8(+) T cells may be one mechanism by which TGF-β plus IL-21, but not IL-6, can drive activated CD8(+) T cells to differentiate into IL-17-producing cells. Taken together, these results provide a novel viewpoint for the plasticity of Tc1 cells.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, ROC. Electronic address: chenhw@nhri.org.tw.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC.
authors.forename: Jy-Ping
authors.initials: JP
authors.lastname: Tsai
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC.
authors.forename: Tsung-You
authors.initials: TY
authors.lastname: Yao
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC.
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan, ROC; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, ROC. Electronic address: levent@nhri.org.tw.
authors.forename: Shin-Jen
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053655:Receptors, Interleukin-21; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D000098546:Interleukin-21
keywords: IL-21; IL-6; T cell plasticity; TGF-β; Tc1; Tc17