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- Title
Pig to rat cell transplantation: reduced cellular and antibody responses to xenografts overexpressing PD-L1.
- Authors
Plege‐Fleck, Annegret; Lieke, Thorsten; Römermann, Dorothee; Düvel, Heike; Hundrieser, Joachim; Buermann, Anna; Kraus, Lilli; Klempnauer, Jürgen; Schwinzer, Reinhard
- Abstract
Background Programmed death-1 ( PD-1) costimulation acts as a negative regulator of T-cell responses to allografts. However, the role of the PD-1 pathway in xenotransplantation is not well defined yet. We have shown previously that human in vitro T-cell responses to porcine transfectants overexpressing PD-Ligand1 ( L23- PD- L1 cells) are remarkably weak. In this report, we asked whether the PD-1/ PD- L1 pathway has the potential to diminish xenogeneic immune responses also in vivo. Methods L23- PD- L1 or mock transfected control cells ( L23- GFP) were transplanted under the kidney capsule of rats. The occurrence of kidney-infiltrating rat leukocytes and the induction of anti-pig antibodies were monitored in grafted animals. Results Assessment of cellular infiltrates revealed similar numbers of macrophages in kidneys grafted with L23- PD- L1 or L23- GFP control cells. However, the level of MHC class- II molecules was reduced on macrophages responding to L23- PD-L1 grafts, suggesting a lower state of activation. Furthermore, less T cells were found in kidneys receiving L23- PD- L1 cells. In addition, the titers of induced anti-pig antibodies were significantly lower in rats grafted with L23- PD- L1 cells. Conclusions These data suggest that signals triggered by PD-1- PD- L1 interaction interfere with activation pathways involved in the induction of cellular and antibody-mediated immune responses to xenografts in vivo. Targeting of PD-1 and/or PD- L1 may be a promising approach for immune modulation after xenotransplantation.
- Subjects
CELL transplantation; ANIMAL models of organ transplants; ANTIBODY formation; XENOGRAFTS; T cells; MACROPHAGES
- Publication
Xenotransplantation, 2014, Vol 21, Issue 6, p533
- ISSN
0908-665X
- Publication type
Article
- DOI
10.1111/xen.12121