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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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 2

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Human TR6 cross-reacts with mouse LIGHT. Human LIGHT-FLAG, mouse LIGHT-F...
Human TR6 cross-reacts with mouse LIGHT. Human LIGHT-FLAG, mouse LIGHT-FLAG and human BLyS-FLAG were expressed in HEK 293T cells. Conditioned supernatants were subjected to immunoblot analysis with an anti-FLAG antibody (top panel). A supernatant from vector-transfected cells was included as a control. The supernatants (20 μl/sample) used represented 5% of the amounts for immunoprecipitation. The supernatants (400 μl) were also subjected to immunoprecipitation either with TR6-Fc (middle panel) or with BCMA-Fc (bottom panel). Immune complexes were resolved by SDS-PAGE and blotted with the anti-FLAG antibody. The prominent bands shown are all of the expected molecular weights of the corresponding recombinant proteins, and the molecular weights are indicated on the left side of the panels. IP, immunoprecipitation.