T-Cell Response in a Cardiac Xenotransplant Model.
Exp Clin Transplant
; 19(7): 708-716, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-34085920
ABSTRACT
OBJECTIVES:
Despite the advances in preclinical cardiac xenotransplantation, the immune reactions caused by species differences are not fully understood. Hyperacute rejection can now be avoided using genetically engineered donor organs, but cellmediated rejection by the adaptive immune response has not been addressed successfully. Here we investigated the initial human pan-T-cell reaction using a pig-human blood working heart model. MATERIALS ANDMETHODS:
Porcine wild-type hearts (n = 7) were perfused with human blood in a biventricular working heart system for 3 hours. As control, blood from the same human donors was circulated without a pig heart. Pan-T cells were selectively extracted from blood taken before and at the end of the perfusion cycle. The relative mRNA expression of selected target genes (real-time quantitative polymerase chain reaction) and the expression of microRNAs were determined.RESULTS:
After xenogeneic organ perfusion, there was a moderate upregulation of several CD4+ marker cytokines (interleukin 2, interleukin 4, interferon γ) compared with control. We found a distinct increase in the mRNA expression of granzyme B and perforin, key markers of cytotoxic T cells. No differences in the marker genes of regulatory T cells were evident. Levels of the anti-inflammatory microRNAs miR-16 and miR-93 were significantly higher in the xenoperfused group than in the control group.CONCLUSIONS:
This study demonstrated that contact of human blood with pig endothelium activates cytotoxic T cells within the first few hours, indicating acute rejection processes. This is accompanied by upregulation of anti-inflammatory microRNAs, which may represent compensatory anti-inflammatory mechanisms.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Corazón
/
MicroARNs
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Exp Clin Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania