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First published online 14 March 2006
doi: 10.1242/jcs.02840
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Research Article |
1 Section for Transplantation Immunology and Immunohematology, Center for Medical Research, University of Tübingen, 72072 Tübingen, Germany
2 Department of Nephrology and Rheumatology, University Hospital Göttingen, 37075 Göttingen, Germany
3 Institute for Physiological Chemistry, Münster University Hospital, 48149 Münster, Germany
4 Department of Neurology, University Hospital Tübingen, 72076 Tübingen, Germany
5 Center for Biochemistry, Department of Dermatology, and Center for Molecular Medicine, University of Cologne, 50931 Cologne, Germany
6 Department of Anatomy and Cell Biology and Faculty of Dentistry, McGill University, Montreal, Quebec H3A 2B2, Canada
7 Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany
8 Center for Molecular Biology of Plants, University of Tübingen, 72076 Tübingen, Germany
9 Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
* Author for correspondence (e-mail: gerd.klein{at}uni-tuebingen.de)
Accepted 15 December 2005
T cells develop in the thymus in a highly specialized cellular and extracellular microenvironment. The basement membrane molecule, laminin-5 (LN-5), is predominantly found in the medulla of the human thymic lobules. Using high-resolution light microscopy, we show here that LN-5 is localized in a bi-membranous conduit-like structure, together with other typical basement membrane components including collagen type IV, nidogen and perlecan. Other interstitial matrix components, such as fibrillin-1 or -2, tenascin-C or fibrillar collagen types, were also associated with these structures. Three-dimensional (3D) confocal microscopy suggested a tubular structure, whereas immunoelectron and transmission electron microscopy showed that the core of these tubes contained fibrillar collagens enwrapped by the LN-5-containing membrane. These medullary conduits are surrounded by thymic epithelial cells, which in vitro were found to bind LN-5, but also fibrillin and tenascin-C. Dendritic cells were also detected in close vicinity to the conduits. Both of these stromal cell types express major histocompatibility complex (MHC) class II molecules capable of antigen presentation. The conduits are connected to blood vessels but, with an average diameter of 2 µm, they are too small to transport cells. However, evidence is provided that smaller molecules such as a 10 kDa dextran, but not large molecules (>500 kDa), can be transported in the conduits. These results clearly demonstrate that a conduit system, which is also known from secondary lymphatic organs such as lymph nodes and spleen, is present in the medulla of the human thymus, and that it might serve to transport small blood-borne molecules or chemokines to defined locations within the medulla.
Key words: Basement membrane, Thymic epithelial cell, Laminin, Reticular network, Antigen presentation
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