VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors

• Published in: Blood 2007-01, Vol.109 (2), p.610-612
• Main Authors: Dasgupta, Suryasarathi, Repessé, Yohann, Bayry, Jagadeesh, Navarrete, Ana-Maria, Wootla, Bharath, Delignat, Sandrine, Irinopoulou, Theano, Kamaté, Caroline, Saint-Remy, Jean-Marie, Jacquemin, Marc, Lenting, Peter J., Borel-Derlon, Annie, Kaveri, Srinivas V., Lacroix-Desmazes, Sébastien
• Format: Article
• Language: English
• Subjects: Antigen Presentation - immunology; Biological and medical sciences; Blood coagulation. Blood cells; Cells, Cultured; Coagulation factors; Dendritic Cells - immunology; Dendritic Cells - ultrastructure; Endocytosis - immunology; Factor VIII - immunology; Fundamental and applied biological sciences. Psychology; Humans; Molecular and cellular biology; T-Lymphocytes - immunology; von Willebrand Factor - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-05-022756

Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in patients with hemophilia A has been evoked but lacks clear cellular and molecular rationale. Here, we demonstrate that VWF protects FVIII from being endocytosed by human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells. The immunoprotective effect of VWF requires a physical interaction with FVIII because the endocytosis of FVIII was significantly restored on hindering the formation of the VWF-FVIII complex. Interestingly, VWF had no direct inhibitory effect either on the ability of DCs to present antigenic peptides or on the activation potency of CD4+ T cells. We thus propose that VWF may reduce the immunogenicity of FVIII by preventing, upstream from the activation of immune effectors, the entry of FVIII in professional antigen-presenting cells.