title: In situ differentiation of CD8αα Τ cells from CD4 T cells in peripheral lymphoid tissues.
abstract: Mutually exclusive cell fate determination of CD4 helper or CD8 killer T cells occurs in the thymus. These T-cell subsets are not believed to redirect other lineages. Here we showed that retinoic acid and transforming growth factor-β1 promoted the differentiation of CD8αα T cells from CD4 T cells in a Runx3-dependent manner. These cells were inferred to belong to immunoregulatory populations because subpopulations of CD8αα+TCRαβ T cells are known to suppress activated T cells, and mice with Runx3(-/-) T cells showed defects during recovery from experimental allergic encephalomyelitis. Our results demonstrate that CD4 T cells play fundamental roles in controlling immune reactions through promotion and attenuation. We accordingly anticipate that clarifying the mechanisms underlying this process will provide insights leading to autoimmune and immunodeficiency disease therapies.
authors.affiliation: Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, 54 Shogoin-Kawahara-cho,Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nambu
authors.forename: Tatsunari
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Jang
authors.forename: Koji
authors.initials: K
authors.lastname: Aoki
authors.forename: Hiroto
authors.initials: H
authors.lastname: Mano
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakano
authors.forename: Motomi
authors.initials: M
authors.lastname: Osato
authors.forename: Katsu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Teramukai
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D059467:Transcriptome
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D016207:Cytokines; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C493730:Runx3 protein, mouse