title: CD8(+) T activation attenuates CD4(+) T proliferation through dendritic cells modification.
abstract: Emerging evidence has suggested that CD8(+) T had modulatory function on CD4(+) T mediated autoimmune and inflammatory diseases. However, the underlying mechanisms remain unclear. In this study, we found that CD8(+) T activation inhibited OVA(323-339) antigen specific CD4(+) T cells proliferation in vitro and in vivo. Further investigation demonstrated that this immunosuppression largely depended on the soluble factor from activated CD8(+) T to modify the phenotype and functions of DCs. Moreover, not only the inhibitors for IDO or iNOS, but also IFN-γ neutralization markedly reversed this immunosuppression on OVA(323-339) antigen specific CD4(+) T cells proliferation. Interestingly, CD8(+) T cells absence aggravated the pathological damage in lung in OVA-induced asthma model, but alleviated by CD8(+) T transfer and activation. Thus, these findings suggested that activated CD8(+) T population exerted feedback regulation in DCs modification, and then attenuated CD4(+) T mediated immune response.
authors.affiliation: Institute of Immunology, Medical Center, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Immunology, Medical Center, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Medical Center, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Medical Center, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. Electronic address: xiasheng1519@163.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xia
authors.affiliation: Institute of Immunology, Medical Center, Tsinghua University, Beijing, People's Republic of China. Electronic address: immunolzhang@gmail.com.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological; D015870:Gene Expression; D007108:Immune Tolerance; D056747:Immunomodulation; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Asthma; CD4(+) T cell; CD8(+) T cell; Dendritic cell; Immune tolerance