Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules.
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.
Drumea-Mirancea
Mihaela
M
Section for Transplantation Immunology and Immunohematology, Center for Medical Research, University of Tübingen, 72072 Tübingen, Germany.
Wessels
Johannes T
JT
Müller
Claudia A
CA
Essl
Mike
M
Eble
Johannes A
JA
Tolosa
Eva
E
Koch
Manuel
M
Reinhardt
Dieter P
DP
Sixt
Michael
M
Sorokin
Lydia
L
Stierhof
York-Dieter
YD
Schwarz
Heinz
H
Klein
Gerd
G
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D002232:Carbocyanines; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002648:Child; D003911:Dextrans / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000648:ultrastructure; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D007211:Indoles; D007797:Laminin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D010047:Ovalbumin / Q000378:metabolism; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D002232:Carbocyanines; D003911:Dextrans; D005456:Fluorescent Dyes; D007211:Indoles; D007797:Laminin; C089187:cyanine dye 3; C007293:DAPI; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate