VSIG4, a B7 family–related protein, is a negative regulator of T cell activation
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
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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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 4

Macrophages in autoimmune infiltrates of the heart do not express VSIG4.

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Macrophages in autoimmune infiltrates of the heart do not express VSIG4....
Myocarditis was induced by immunization with α–myosin heavy chain–derived peptide in CFA (CFA/Myhca), and as a control, untreated mice were used. Heart sections from inflamed hearts and control hearts were stained with VSIG4 (green) together with CD68, MHC class II (MHC II), or CD11b (red) as indicated. In untreated mice, a fraction of CD68- or CD11b-positive tissue-resident macrophages coexpressed VSIG4. (Note that all VSIG4-positive cells coexpressed Cd11b; in some cases, Cd11b expression was low, precluding visualization of the expression in an overlay image). In contrast, MHC class II–positive DCs showed no coexpression of VSIG4. In CFA/Myhca-immunized mice, inflammatory foci included numerous CD68-positive macrophages that showed no coexpression of VSIG4. Occasional VSIG4-positive macrophages were detected in the myocardium surrounding the inflammatory focus. On a consecutive histological section, abundant MHC class II expression was detected within the inflammatory infiltrate, probably mostly on activated macrophages. Representative stainings of at least 2 independent experiments are shown. Original magnification, ×150.