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PMID: 17016562 Published · ppublish English Journal Article

VSIG4, a B7 family-related protein, is a negative regulator of T cell activation.

The Journal of clinical investigation ·Vol. 116 ·No. 10 ·2006-10-00 ·Pages 2817-26

Vogt L, Schmitz N, Kurrer MO, Bauer M, Hinton HI, Behnke S, Gatto D, Sebbel P, Beerli RR, Sonderegger I, Kopf M, Saudan P, Bachmann MF

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.

MeSH Terms
Amino Acid Sequence Animals Autoimmune Diseases/chemically induced,immunology,metabolism B7-1 Antigen/pharmacology B7-H1 Antigen Cell Line Cell Proliferation/drug effects Female Gene Expression/drug effects,immunology Humans Immunoglobulins/genetics,pharmacology,physiology Interferon-gamma/metabolism Interleukin-2/metabolism,pharmacology Lipopolysaccharides/pharmacology Liver/cytology,metabolism Lymphocyte Activation/drug effects,immunology Macrophages/drug effects,metabolism Membrane Glycoproteins/pharmacology Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data Myocarditis/chemically induced,immunology,metabolism Peptides/pharmacology Programmed Cell Death 1 Ligand 2 Protein Receptors, Complement/genetics,metabolism,physiology Sequence Homology, Amino Acid T-Lymphocytes/drug effects,immunology,metabolism Thioglycolates/pharmacology
Chemicals
B7-1 Antigen B7-H1 Antigen Cd274 protein, mouse Immunoglobulins Interleukin-2 Lipopolysaccharides Membrane Glycoproteins PDCD1LG2 protein, human Pdcd1lg2 protein, mouse Peptides Programmed Cell Death 1 Ligand 2 Protein Receptors, Complement Thioglycolates VSIG4 protein, human VSIG4 protein, mouse Interferon-gamma
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Vogt Lorenz
Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
Schmitz Nicole
Kurrer Michael O
Bauer Monika
Hinton Heather I
Behnke Silvia
Gatto Dominique
Sebbel Peter
Beerli Roger R
Sonderegger Ivo
Kopf Manfred
Saudan Philippe
Bachmann Martin F
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI25673
Published
2006-10-00
Pages
2817-26
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1578631
Subset
IM
Databases
RefSeq
NM_177789
Corrections
CommentIn
PMID: 17016555
External Links
PubMed source DOI: 10.1172/JCI25673 PMC Full Text View journal details
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