title: Specificity of regulatory CD4+CD25+ T cells for self-T cell receptor determinants.
abstract: Although the phenotypic and regulatory properties of the CD4(+)CD25(+) T cell lineage (Treg cells) have been well described, the specificities remain largely unknown. We demonstrate here that the CD4(+)CD25(+) Treg population includes the recognition of a broad spectrum of human TCR CDR2 determinants found in the germline V gene repertoire as well as that of a clonotypic nongermline-encoded CDR3beta sequence present in a recombinant soluble T cell receptor (TCR) protein. Regulatory activity was demonstrated in T cell lines responsive to TCR but not in T cell lines responsive to control antigens. Inhibitory activity of TCR-reactive T cells required cell-cell contact and involved CTLA-4, GITR, IL-10, and IL-17. Thus, the T-T regulatory network includes Treg cells with specificity directed toward self-TCR determinants.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA. buenafea@ohsu.edu
authors.forename: Abigail C
authors.initials: AC
authors.lastname: Buenafe
authors.forename: Laura
authors.initials: L
authors.lastname: Tsaknaridis
authors.forename: Leslie
authors.initials: L
authors.lastname: Spencer
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Hicks
authors.forename: Rachel H
authors.initials: RH
authors.lastname: McMahan
authors.forename: Lisa
authors.initials: L
authors.lastname: Watson
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Culbertson
authors.forename: Dorian
authors.initials: D
authors.lastname: Latocha
authors.forename: Keith
authors.initials: K
authors.lastname: Wegmann
authors.forename: Tom
authors.initials: T
authors.lastname: Finn
authors.forename: Richard
authors.initials: R
authors.lastname: Bartholomew
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Burrows
authors.forename: Ruth
authors.initials: R
authors.lastname: Whitham
authors.forename: Dennis N
authors.initials: DN
authors.lastname: Bourdette
authors.forename: Richard E
authors.initials: RE
authors.lastname: Jones
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.forename: Yuan K
authors.initials: YK
authors.lastname: Chou
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D003001:Cloning, Molecular; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000502:physiology; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D007165:Immunosuppression Therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016622:Silver Staining
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins