Copyright © 2006, European Society of Cardiology
An anti-major histocompatibility complex class I intrabody protects endothelial cells from an attack by immune mediators
aInstitute of Medical Immunology, Charité Universitätsmedizin Berlin, Monbijoustr. 2a, D-10117 Berlin, Germany
bLouisiana State University Health Sciences Center, Gene Therapy Program, 533 Bolivar Street CSRB 606 New Orleans, LA 70112, USA
cDivision of Pathology and Laboratory Medicine, Veterans Affairs Puget Sound Health Care System, 1660 Columbian Way, Seattle, WA 98108, USA
* Corresponding author. Tel.: +49 30 450524198; fax: +49 30 450524907. Email address: martina.seifert{at}charite.de
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 
-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 -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.
KEYWORDS Endothelial cell; Gene therapy; Intrabody; Tissue engineering
1 Current address: Experimental Rheumatology, Charité Universitätsmedizin Berlin, c/o DRFZ, Charitéplatz 1, 10117 Berlin, Germany.