title: Spatial and molecular organization of lymph node T cell cortex: a labyrinthine cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix.
abstract: Naive T cells encounter antigen-presenting cells within the cortex of lymph nodes to initiate primary immune responses. Within this T cell cortex is the reticular network (RN)--a system of collagen fibers and extracellular matrix (ECM) wrapped by fibroblastic reticular cells (FRC). We have investigated the distribution of various molecules, including ECM proteins and proteoglycans, in the T cell cortex of both human and rodent lymph node. We confirm and extend reports of matrix elements in the RN. In addition, we find that staining for the laminin-alpha3 chain and for tenascin reveals a 'hollow' reticular pattern, consistent with localization to the basement membrane-like covering of reticular fibers. In contrast, keratan sulfate is observed in a fine linear pattern within the RN, suggesting it is localized to the core of the fibers. Staining with the marker ER-TR7 indicates that FRC cover all identifiable ECM surfaces of the T cell cortex. Based on these findings and previous reports, we conclude that cortical lymphocytes migrate within a 'labyrinthine cavity' free of fibrillar ECM, distinguishing the T cell cortex from other loose connective tissues, and that the FRC lining of the cavity constitutes an epithelium-like boundary. We propose that this spatial organization facilitates ameboid leukocyte crawling along preformed paths of least resistance and that the basement membrane-like ECM of the FRC may facilitate fluid transport within the RN by limiting leakage from the fiber.
authors.affiliation: Pathobiology, Pfizer Global Research & Development, and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Kaldjian
authors.forename: J E
authors.initials: JE
authors.lastname: Gretz
authors.forename: A O
authors.initials: AO
authors.lastname: Anderson
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: S
authors.initials: S
authors.lastname: Shaw
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000302:isolation & purification; D003094:Collagen / Q000302:isolation & purification; D004847:Epithelial Cells / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000302:isolation & purification; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D008198:Lymph Nodes / Q000648:ultrastructure*; D051379:Mice; D011509:Proteoglycans / Q000302:isolation & purification; D051381:Rats; D013601:T-Lymphocytes / Q000648:ultrastructure*; D019063:Tenascin / Q000302:isolation & purification; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D003094:Collagen; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D019063:Tenascin; D000097794:Kalinin