Lentivirus-mediated PD-L1 overexpression in bone marrow-derived dendritic cells induces immune tolerance in a rat keratoplasty model.
Transpl Immunol
; 74: 101654, 2022 10.
Article
in En
| MEDLINE
| ID: mdl-35777615
ABSTRACT
PURPOSE:
The side effects of immune suppressants on immune rejection have become increasingly apparent after keratoplasty. To find out new alternative immunotherapy strategies, we studied the role of programmed death-1 (PD-1) and its ligand (PD-L1) co-stimulatory pathway in inducing immune tolerance of rat keratoplasty.METHODS:
The PD-L1 protein was constitutively overexpressed via lentiviral transduction in bone marrow-derived dendritic cells (BMDCs) from rats, then infused via the tail vein into rats before undergoing keratoplasty. Western blot analysis of PD-L1 protein confirmed the effectiveness of lentivirus-mediated. The phenotype of immature BMDC was confirmed by flow cytometry analysis with CD80, CD86, CD11c and MHC-II antibodies. To investigate the mechanism of the immune tolerance induced by BMDCs transfusion, PD-L1, IFN-γ and IL-17 in serum and cell culture supernatant were assessed by ELISA and qPCR.RESULTS:
After LPS stimulation, immature dendritic cells with over-expression of PD-L1 still showed high expression of PD-L1(p < 0.001), and low expression of IL-17 and IFN-γ (p < 0.001), which reduced neovascularization (p < 0.05), and prolonged the survival after corneal implants.CONCLUSION:
Immature DC cells with overexpression of PD-L1 have low ability to activate T cellsï¼which is a potential treatment for avoiding graft rejection by promoting natural immunosuppression. This cellular treatment is expected to reduce the use of immune suppressants and the occurrence of side effects.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Corneal Transplantation
/
B7-H1 Antigen
Limits:
Animals
Language:
En
Journal:
Transpl Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
/
TRANSPLANTE
Year:
2022
Document type:
Article
Affiliation country:
China