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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.

Original publication

DOI

10.1172/JCI25673

Type

Journal article

Journal

J Clin Invest

Publication Date

10/2006

Volume

116

Pages

2817 - 2826

Keywords

Amino Acid Sequence, Animals, Autoimmune Diseases, B7-1 Antigen, B7-H1 Antigen, Cell Line, Cell Proliferation, Female, Gene Expression, Humans, Immunoglobulins, Interferon-gamma, Interleukin-2, Lipopolysaccharides, Liver, Lymphocyte Activation, Macrophages, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Myocarditis, Peptides, Programmed Cell Death 1 Ligand 2 Protein, Receptors, Complement, Sequence Homology, Amino Acid, T-Lymphocytes, Thioglycolates