An anti-major histocompatibility complex class I intrabody protects endothelial cells from an attack by immune mediators.
Cardiovasc Res
; 72(2): 331-8, 2006 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-16963004
ABSTRACT
OBJECTIVE:
In vitro endothelialization has significantly improved the overall outcome of artificial prostheses in cardiovascular bypass surgery. A drawback of this tissue-engineering method remains the limited availability of suitable autologous endothelial cells (EC), especially in aged patients. Allogeneic EC with high proliferative capacity represent a potentially valuable alternative to a patient-specific vascular transplant. However, such cells carry the risk of being rejected due to Major Histocompatibility Complex (MHC) mismatches.METHODS:
We investigated the effects of a very potent, intracellularly expressed antibody directed against MHC class I molecules, referred to as alpha-rat MHC I single chain variable fragment (sFv) intrabody. The intrabody was stably expressed in rat aortic EC (RAEC) following lentiviral vector-mediated gene transfer. The functional consequence of the MHC I down-regulation was tested in an allogeneic setting in two different in vitro assays.RESULTS:
Stable expression of the alpha-rat MHC I sFv intrabody resulted in a highly efficient depletion of surface MHC I. Thereby those RAEC which displayed low MHC I levels over extended periods of time were protected against killing by allo-specific, cytotoxic T cells (CTL) and by allo-antibody/complement-mediated lysis.CONCLUSIONS:
These results demonstrate that intrabody-mediated down-regulation of MHC I reduces the immunogenicity of RAEC which may provide a suitable alternative supply for the lining of vascular prostheses.
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Bases de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Antígenos de Histocompatibilidad Clase I
/
Células Endoteliales
/
Factores Inmunológicos
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Año:
2006
Tipo del documento:
Article
País de afiliación:
Alemania