title: VSIG4, a B7 family-related protein, is a negative regulator of T cell activation.
abstract: T cell activation by APCs is positively and negatively regulated by members of the B7 family. We have identified a previously unknown function for B7 family-related protein V-set and Ig domain-containing 4 (VSIG4). In vitro experiments using VSIG4-Ig fusion molecules showed that VSIG4 is a strong negative regulator of murine and human T cell proliferation and IL-2 production. Administration to mice of soluble VSIG4-Ig fusion molecules reduced the induction of T cell responses in vivo and inhibited the production of Th cell-dependent IgG responses. Unlike that of B7 family members, surface expression of VSIG4 was restricted to resting tissue macrophages and absent upon activation by LPS or in autoimmune inflammatory foci. The specific expression of VSIG4 on resting macrophages in tissue suggests that this inhibitory ligand may be important for the maintenance of T cell unresponsiveness in healthy tissues.
authors.affiliation: Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Vogt
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitz
authors.forename: Michael O
authors.initials: MO
authors.lastname: Kurrer
authors.forename: Monika
authors.initials: M
authors.lastname: Bauer
authors.forename: Heather I
authors.initials: HI
authors.lastname: Hinton
authors.forename: Silvia
authors.initials: S
authors.lastname: Behnke
authors.forename: Dominique
authors.initials: D
authors.lastname: Gatto
authors.forename: Peter
authors.initials: P
authors.lastname: Sebbel
authors.forename: Roger R
authors.initials: RR
authors.lastname: Beerli
authors.forename: Ivo
authors.initials: I
authors.lastname: Sonderegger
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Philippe
authors.initials: P
authors.lastname: Saudan
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000494:pharmacology; D060890:B7-H1 Antigen; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007136:Immunoglobulins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011951:Receptors, Complement; D013864:Thioglycolates; C414427:VSIG4 protein, human; C509992:VSIG4 protein, mouse; D007371:Interferon-gamma