Modulation of T-cell responses to alloantigens by TR6/DcR3.
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.
Mesh Terms:
Animals, Cell Line, Female, Flow Cytometry, Granulocyte-Macrophage Colony-Stimulating Factor, Heart Transplantation, Humans, Immunoblotting, Interferon-alpha, Interleukin-10, Interleukin-6, Isoantigens, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Precipitin Tests, Receptors, Cell Surface, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Member 6b, Recombinant Fusion Proteins, Spleen, T-Lymphocytes, Tumor Necrosis Factor Ligand Superfamily Member 14, Tumor Necrosis Factor-alpha
Animals, Cell Line, Female, Flow Cytometry, Granulocyte-Macrophage Colony-Stimulating Factor, Heart Transplantation, Humans, Immunoblotting, Interferon-alpha, Interleukin-10, Interleukin-6, Isoantigens, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Precipitin Tests, Receptors, Cell Surface, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Member 6b, Recombinant Fusion Proteins, Spleen, T-Lymphocytes, Tumor Necrosis Factor Ligand Superfamily Member 14, Tumor Necrosis Factor-alpha
J. Clin. Invest.
Date: Jun. 01, 2001
PubMed ID: 11390428
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