A Novel Pseudovirus Containing Lewis X Oligosaccharides With pD-L1 Targeting to DCs Induces T Cells Tolerance

Abstract

The purpose of this study was to assess the potential of a novel pseudovirus targeting to dendritic cells (DCs) inducing T cells tolerance. To prove it, allogeneic DCs transfected of the novel pseudovirus containing Lewis X oligosaccharides with programmed death-ligand 1 were co-cultured with T cells. After mixed leukocyte reactions were performed, the proliferation, cytokines secretion, and activation marker expression of T cells were analyzed. The results demonstrated that the proliferation, cytokines secretion, and activation marker expression of T cells were suppressed after co-cultured with the pseudovirus transfected DCs. These findings suggested that DCs transfected with pseudovirus could induce T-cells tolerance, which provided a promising therapeutic means to negatively manipulate immune response in organ transplantation.

Layers of regulation in induction of mixed chimerism by anti-CD40L

“…Overall, these findings provide a framework from which to build a clinically applicable chimerism induction regimen by targeting the PD-1, CTLA-4, LAG-3 and TGFβ pathways. For example, use of PD-L1.Ig or transfection of donor BMCs with PD-L1 16,17 and PD-L2 may represent a viable strategy to support T-cell tolerance at the time of BMT. Importantly, exposure of naïve T cells to antigen without costimulation but in the presence of TGFβ results in activation of the NFAT transcription factor but not AP-1 or NFκB, which can set up a feedback loop that heightens the tolerogenic effects of TGFβ.…”