title: The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses.
abstract: We investigated the in vivo function of the B7 family member B7-H3 (also known as B7RP-2) by gene targeting. B7-H3 inhibited T cell proliferation mediated by antibody to T cell receptor or allogeneic antigen-presenting cells. B7-H3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which T helper cells differentiated toward type 1 (T(H)1) rather than type 2 (T(H)2). B7-H3 expression was consistently enhanced by interferon-gamma but suppressed by interleukin 4 in dendritic cells. B7-H3-deficient mice developed experimental autoimmune encephalomyelitis several days earlier than their wild-type littermates, and accumulated higher concentrations of autoantibodies to DNA. Thus, B7-H3 is a negative regulator that preferentially affects T(H)1 responses.
authors.affiliation: Advanced Medical Discovery Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada. wsuh@uhnres.utoronto.ca
authors.forename: Woong-Kyung
authors.initials: WK
authors.lastname: Suh
authors.forename: Beata U
authors.initials: BU
authors.lastname: Gajewska
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okada
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gronski
authors.forename: Edward M
authors.initials: EM
authors.lastname: Bertram
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dawicki
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Duncan
authors.forename: Jacob
authors.initials: J
authors.lastname: Bukczynski
authors.forename: Suzanne
authors.initials: S
authors.lastname: Plyte
authors.forename: Andrew
authors.initials: A
authors.lastname: Elia
authors.forename: Andrew
authors.initials: A
authors.lastname: Wakeham
authors.forename: Annick
authors.initials: A
authors.lastname: Itie
authors.forename: Stephen
authors.initials: S
authors.lastname: Chung
authors.forename: Joan
authors.initials: J
authors.lastname: Da Costa
authors.forename: Sudha
authors.initials: S
authors.lastname: Arya
authors.forename: Tom
authors.initials: T
authors.lastname: Horan
authors.forename: Pauline
authors.initials: P
authors.lastname: Campbell
authors.forename: Kevin
authors.initials: K
authors.lastname: Gaida
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Tania H
authors.initials: TH
authors.lastname: Watts
authors.forename: Steven K
authors.initials: SK
authors.lastname: Yoshinaga
authors.forename: Mark R
authors.initials: MR
authors.lastname: Bray
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
chemical_list: D001323:Autoantibodies; D060887:B7 Antigens; D018122:B7-1 Antigen; C486038:Cd276 protein, mouse; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma