Pigs expressing the human inhibitory ligand PD-L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties.
Xenotransplantation
; 25(5): e12387, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29446180
ABSTRACT
BACKGROUND:
The programmed cell death-1 (PD-1, CD279)/PD-Ligand1 (PD-L1, CD274) receptor system is crucial for controlling the balance between immune activation and induction of tolerance via generation of inhibitory signals. Expression of PD-L1 is associated with reduced immunogenicity and renders cells and tissues to an immune-privileged/tolerogenic state.METHODS:
To apply this concept for clinical xenotransplantation, we generated human (h)PD-L1 transgenic pigs and characterized expression and biological function of the transgene at the cellular level.RESULTS:
The hPD-L1 was detected in kidney, heart, and pancreas. In addition, peripheral blood mononuclear cells (PBMC), cultured fibroblasts, and endothelial cells were hPD-L1 positive (hPD-L1+ ). The hPD-L1 levels were increased by the treatment of transgenic cells with human cytokines (eg, TNF-α), suggesting a regulatable mode of transgene expression. Compared to cells from wild-type pigs, hPD-L1+ PBMC had a significantly reduced capacity to stimulate proliferation of human CD4+ T cells. Moreover, fibroblasts from hPD-L1 transgenic pigs were partially protected from cell-mediated lysis by human cytotoxic effector cells.CONCLUSIONS:
These data indicate a low immunogenic, immune-protected status of cells from hPD-L1 transgenic pigs. The integration of the hPD-L1 concept into existing multi-transgenic pigs is promising to achieve long-term survival of porcine xenografts in non-human primate recipients.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Animales Modificados Genéticamente
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Leucocitos Mononucleares
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Linfocitos T
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Antígeno B7-H1
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Xenoinjertos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Xenotransplantation
Asunto de la revista:
TRANSPLANTE
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania