title: IL-4 induces a suppressive IL-10-producing CD8+ T cell population via a Cdkn2a-dependent mechanism.
abstract: CD8(+) T cells play an important role in immune regulation and effective immune responses against tumor cells, viral infection, and intracellular pathogens. In this report, using tiger or 10BiT mice, we defined a population of IL-10-producing CD8(+) T cells that were induced by IL-4. These IL-10(+)CD8(+) T cells possessed a strong inhibitory effect on the CD4(+) T cell proliferation in an IL-10-dependent and cell contact-dependent fashion. In comparison with IL-10(-)CD8(+) T cells, IL-10(+)CD8(+) T cells expressed an array of Th2-like cytokines (IL-4, IL-5), perforin, and granzymes, as well as the cell cycle regulatory protein Cdkn2a. Interestingly, knockdown of cdkn2a using siRNA reduced IL-4-induced IL-10 production significantly. Furthermore, CD8(+) T cells from Cdkn2a(-/-) mice produced a significantly lower amount of IL-10, and the effect was limited to CD8(+) T cells but not observed in CD4(+) T cells and APCs. Finally, IL-10(+)CD8(+) T cells played a protective role in the TNBS-induced murine colitis model, indicating a critical role of this population of CD8(+) T cells in regulatory immune responses. Taken together, we have defined a population of IL-10-producing CD8(+) Tregs induced by IL-4 and mediated by Cdkn2a.
authors.affiliation: 2.College of Life Sciences, Nankai University, Tianjin 300071, China. yinzn@nankai.edu.cn or lqzhao@nankai.edu.cn.
authors.forename: Yapu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhao
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Sun
authors.forename: Jianlei
authors.initials: J
authors.lastname: Hao
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qi
authors.forename: Xinglong
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Puyue
authors.initials: P
authors.lastname: Wang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; C556062:IL10 protein, mouse; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4
keywords: differentiation; suppression; transcription factor