Modulation of T-cell responses to alloantigens by TR6/DcR3
Jun Zhang, … , Paul A. Moore, Jiangping Wu
Jun Zhang, … , Paul A. Moore, Jiangping Wu
Published June 1, 2001
Citation Information: J Clin Invest. 2001;107(11):1459-1468. https://doi.org/10.1172/JCI12159.
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Article

Modulation of T-cell responses to alloantigens by TR6/DcR3

Abstract

TR6 (DcR3) is a new member of the TNF receptor (TNFR) family that lacks a transmembrane domain in its sequence, indicating that it is a secreted molecule. TR6 can bind to FasL and prevent FasL-induced apoptosis; it can also associate with LIGHT, another TNF family member. The role of TR6 in immune responses was investigated in this study. According to flow cytometry, recombinant human TR6-Fc binds to human LIGHT expressed on 293 cells or on activated human T cells and competes with the LIGHT receptor TR2 for the binding to LIGHT on these cells. Human TR6 could cross-react with mouse LIGHT in immunoprecipitation. TR6-Fc also downregulates cytotoxic T lymphocyte activity in vitro and graft-versus-host responses in mice. Moreover, TR6-Fc modulates lymphokine production by alloantigen-stimulated mouse T cells. TR6-Fc ameliorated rejection response to mouse heart allograft. These results indicate that TR6 can dampen T-cell responses to alloantigens. Such regulatory effects of TR6 probably occur via interference with interaction between pairs of related TNF and TNFR family members, LIGHT/TR2 being one of the possible candidate pairs.

Authors

Jun Zhang, Theodora W. Salcedo, Xiaochun Wan, Stephen Ullrich, Bugen Hu, Theresa Gregorio, Ping Feng, Shijie Qi, Huifang Chen, Yun Hee Cho, Yuling Li, Paul A. Moore, Jiangping Wu

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Figure 1

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TR-6 binds to cell surface LIGHT and competes with TR2 for its binding t...
TR-6 binds to cell surface LIGHT and competes with TR2 for its binding to LIGHT. (a) Flow cytometry on LIGHT-expressing 293 cells. LIGHT-expressing 293 transfectants or untransfected 293 cells were incubated with TR2-Fc, TR6-Fc, or a control protein TR11-Fc (50 ng/sample), and binding was detected with a PE-conjugated goat anti-human Ig antibody by flow cytometry. Solid lines: LIGHT-expressing 293 cells; shaded areas: untransfected 293 cells. Top row: cells were stained in the absence of competitors; middle and bottom rows: cells were stained in the presence of 10 μg non-Fc TR6 or LIGHT, respectively, as competitors. (b) Flow cytometry on human T cells. Human T cells were activated as described in Methods. Binding of TR2-Fc, TR6-Fc, or TR11-Fc (50 ng/sample) with T cells was detected by flow cytometry using the PE-conjugated goat anti-human Ig antibody. Solid lines: T cells activated with anti-CD3 followed by ionomycin and PMA; shaded area: nonactivated T cells. Top row: cells were stained in the absence competitors; middle and bottom rows: cells were stained in the presence of 10 μg non-FC TR6 or LIGHT, respectively, as competitors.