title: Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells.
abstract: The antigenic targets recognized by naturally occurring CD4(+) CD25(+) regulatory T cells (T reg cells) have been elusive. We have serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas by serological identification of antigens by recombinant expression cloning (SEREX). CD4(+) CD25(+) T cells from mice immunized with SEREX-defined self-antigens had strong suppressive activity on peptide-specific proliferation of CD4(+) CD25(-) T cells and CD8(+) T cells. The suppressive effect was observed without in vitro T cell stimulation. Foxp3 expression in these CD4(+) CD25(+) T cells from immunized mice was 5-10 times greater than CD4(+) CD25(+) T cells derived from naive mice. The suppressive effect required cellular contact and was blocked by anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene antibody. In vitro suppressive activity essentially disappeared 8 wk after the last immunization. However, it was regained by in vitro restimulation with cognate self-antigen protein but not with control protein. We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4(+) CD25(+) T reg cells.
authors.affiliation: Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
authors.forename: Isao
authors.initials: I
authors.lastname: Tawara
authors.forename: Kanako
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Kagemasa
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D007108:Immune Tolerance; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology*
chemical_list: D001324:Autoantigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2