TR6-Fc significantly prolonged the mean survival time of mouse heart allografts to 10.0 days compared to 6.8 days in buffer-treated controls.
Does TR6-Fc modulate T-cell responses to alloantigens and ameliorate heart allograft rejection in preclinical models?
TR6-Fc dampens T-cell responses to alloantigens and ameliorates heart allograft rejection in mouse models, suggesting potential as an immunosuppressive agent.
Absolute Event Rate: 10% vs 6.8%
p-value: p=0.0002
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.
Zhang et al. (Fri,) conducted a other in Allograft rejection and Graft-versus-host disease (Preclinical models). TR6-Fc vs. Buffer or MCIF-Fc was evaluated on Mean survival time of heart allografts in mice (days) (p=0.0002). TR6-Fc significantly prolonged the mean survival time of mouse heart allografts to 10.0 days compared to 6.8 days in buffer-treated controls.