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

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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-α3 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.

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