Lymphatic Vessels in the Development of Tissue and Organ Rejection
The lymphatic vascular system—amongst other tasks—is critically involved in the regulation of adaptive immune responses as it provides an important route for APC trafficking to secondary lymphatic organs. In this context, the cornea, which is the transpar
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Lymphatic Vessels in the Development of Tissue and Organ Rejection Deniz Hos and Claus Cursiefen
Abstract The lymphatic vascular system—amongst other tasks—is critically involved in the regulation of adaptive immune responses as it provides an important route for APC trafficking to secondary lymphatic organs. In this context, the cornea, which is the transparent and physiologically avascular “windscreen” of the eye, has served as an excellent in vivo model to study the role of the blood and lymphatic vasculature in mediating allogenic immune responses after transplantation. Especially the mouse model of high-risk corneal transplantation, where corneal avascularity is abolished by a severe inflammatory stimulus prior to keratoplasty, allows for comparison to other transplantations performed in primarily vascularized tissues and solid organs. Using this model, we recently demonstrated that especially lymphatic vessels, but not blood vessels, define the high-risk status of vascularized corneas and that anti(lymph)angiogenic treatment significantly promotes corneal allograft survival. Since evidence for lymphangiogenesis and its potential association with graft rejection is nowadays also present in solid organ transplantation, studies are currently addressing the potential benefits of anti(lymph)angiogenic treatment as a novel therapeutic concept also in solid organ grafting with promising initial results.
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Introduction
The lymphatic vascular system is essential for fluid homeostasis and the resorption of dietary fats and is also involved in the regulation of inflammation, immune surveillance, and induction of adaptive immunity (Alitalo 2011; Alitalo et al. 2005;
All authors declare no financial disclosures. D. Hos • C. Cursiefen (*) Department of Ophthalmology, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany e-mail: [email protected] F. Kiefer and S. Schulte-Merker (eds.), Developmental Aspects of the Lymphatic Vascular System, Advances in Anatomy, Embryology and Cell Biology 214, DOI 10.1007/978-3-7091-1646-3_10, © Springer-Verlag Wien 2014
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Potente et al. 2011; Tammela and Alitalo 2010). Generally, for the initiation of adaptive immune responses to foreign antigens, mature antigen-presenting cells (APCs) with high expression of major histocompatibility (MHC) class II from the periphery must interact with and prime naı¨ve, resident T lymphocytes in lymph nodes. In this context, lymphatic vessels provide important paths for APC trafficking and for access of soluble antigens to the secondary lymphatic organs (Alitalo 2011; Dana 2006; Randolph et al. 2005). Immunity to foreign antigens is essential to maintain the integrity of the organism. After organ or tissue transplantation, however, immune responses are undesired as the organism critically depends on graft function. Although the role of the lymphatic vasculature has extensively been studied in the context of adaptive immunity (Randolph et al. 2005), its involvement in allogenic immune respons
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