Pig to rat cell transplantation: reduced cellular and antibody responses to xenografts overexpressing PD-L1.
| Autor: | Plege-Fleck A; Transplant Laboratory, Department of General-, Visceral-, and Transplantation Surgery, Hannover Medical School, Hannover, Germany., Lieke T, Römermann D, Düvel H, Hundrieser J, Buermann A, Kraus L, Klempnauer J, Schwinzer R |
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| Jazyk: | angličtina |
| Zdroj: | Xenotransplantation [Xenotransplantation] 2014 Nov-Dec; Vol. 21 (6), pp. 533-42. Date of Electronic Publication: 2014 Jul 09. |
| DOI: | 10.1111/xen.12121 |
| Abstrakt: | 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. (© 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.) |
| Databáze: | MEDLINE |
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