Characterization of a conduit system containing laminin-5 in the human thymus

TY - JOUR

T1 - Characterization of a conduit system containing laminin-5 in the human thymus

T2 - a potential transport system for small molecules

AU - Drumea-Mirancea, Mihaela

AU - Wessels, Johannes T

AU - Müller, Claudia A

AU - Essl, Mike

AU - Eble, Johannes A

AU - Tolosa, Eva

AU - Koch, Manuel

AU - Reinhardt, Dieter P

AU - Sixt, Michael

AU - Sorokin, Lydia

AU - Stierhof, York-Dieter

AU - Schwarz, Heinz

AU - Klein, Gerd

PY - 2006/4/1

Y1 - 2006/4/1

N2 - 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 mum, 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.

AB - 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 mum, 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.

KW - Antibodies, Monoclonal

KW - Antigen-Presenting Cells

KW - Basement Membrane

KW - Biological Transport

KW - Carbocyanines

KW - Cell Adhesion

KW - Cell Culture Techniques

KW - Cells, Cultured

KW - Child

KW - Dextrans

KW - Epithelial Cells

KW - Fluorescein-5-isothiocyanate

KW - Fluorescent Dyes

KW - Humans

KW - Imaging, Three-Dimensional

KW - Immunohistochemistry

KW - Indoles

KW - Laminin

KW - Models, Biological

KW - Ovalbumin

KW - Precipitin Tests

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Thymus Gland

U2 - 10.1242/jcs.02840

DO - 10.1242/jcs.02840

M3 - SCORING: Journal article

C2 - 16537647

VL - 119

SP - 1396

EP - 1405

JO - J CELL SCI

JF - J CELL SCI

SN - 0021-9533

IS - Pt 7

ER -