VSIG4, a B7 family-related protein, is a negative regulator of T cell activation.
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.
Vogt
Lorenz
L
Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
Schmitz
Nicole
N
Kurrer
Michael O
MO
Bauer
Monika
M
Hinton
Heather I
HI
Behnke
Silvia
S
Gatto
Dominique
D
Sebbel
Peter
P
Beerli
Roger R
RR
Sonderegger
Ivo
I
Kopf
Manfred
M
Saudan
Philippe
P
Bachmann
Martin F
MF
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
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