VSIG4, a B7 family–related protein, is a negative regulator of T cell activation
Lorenz Vogt, … , Philippe Saudan, Martin F. Bachmann
Lorenz Vogt, … , Philippe Saudan, Martin F. Bachmann
Published October 2, 2006
Citation Information: J Clin Invest. 2006;116(10):2817-2826. https://doi.org/10.1172/JCI25673.
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Research Article Immunology

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

Lorenz Vogt, Nicole Schmitz, Michael O. Kurrer, Monika Bauer, Heather I. Hinton, Silvia Behnke, Dominique Gatto, Peter Sebbel, Roger R. Beerli, Ivo Sonderegger, Manfred Kopf, Philippe Saudan, Martin F. Bachmann

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Figure 3

VSIG4 is expressed on resting tissue macrophages.

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VSIG4 is expressed on resting tissue macrophages. Organs of untreated mi...
Organs of untreated mice were assessed for VSIG4 expression by histology. (A and E) Kupffer cells lining the sinusoids of the liver were evenly positive for VSIG4. (B and F) Occasional macrophages of the red pulp of the spleen were positive, while macrophages of the white pulp were negative for VSIG4 (B). Within the red pulp (F), iron-laden macrophages (a weak granular signal was derived from the iron) were negative (small arrow), while other macrophages were weakly positive for VSIG4 (large arrowheads). (C and G) The myocardium showed an uneven distribution of VSIG4-positive macrophages. VSIG4 was also detected in tissue-resident macrophages of adipose tissue (D). VSIG4 was absent in thymic cortex and detected in rare macrophages of the thymic medulla (H). Representative stainings of at least 2 independent experiments are shown. Original magnification, ×60 (A–D); ×150 (E–H).