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.

Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection

“…Integral to this, antigen, antigen-presenting cells, and specific lymphocytes must come together in the lymphoid organs. Much of this may be facilitated by the surrounding reticular network, which forces close interaction between migrating T cells and local antigen-presenting cells (11,28), enables the rapid transport and presentation of antigens through the FRC conduit network (20,21,26), and controls the recruitment and local migration of lymphocytes via presentation of chemokines (13). Targeting of FRC by LCMV CL-13 has potential consequences for the structural integrity of the reticular network and its overall function.…”

Cellular Interactions in Lymph Node Development

“…As such, the organizer cells identified in developing lymph nodes could be viewed as myofibroblasts: they produce chemokines and express ICAM-1 and VCAM-1 upon LT␤R triggering. Furthermore, in adult lymph nodes, the expression of vimentin has been observed in reticular fibroblasts that colocalize with many extracellular matrix components (52,53). Therefore, it is highly likely that the capacity of organizer cells to attract hemopoietic cells and orchestrate their spatial positioning during lymphoid organogenesis is a role that myofibroblasts fulfill in inflammatory lesions.…”

Antigen-Specific Lymphocyte Sequestration in Lymphoid Organs: Lack of Essential Roles for αL and α4 Integrin-Dependent Adhesion or Gαi Protein-Coupled Receptor Signaling

“…This treatment was combined with a blocking mAb against the ␣ 4 integrin chain (17), which can pair with ␤ 1 to form a receptor for VCAM-1 and fibronectin. We reasoned that combined treatment with blocking mAb against both ␣ L and ␣ 4 would allow us to test not only the idea that sequestration is mediated by T cell adhesion to APCs, but also the hypothesis that activated T cells are retained in secondary lymphoid organs by adhesion to extracellular components of the lymph node microenvironment (5,18).…”