Immunology Letters 138 (2011) 9–11 Contents lists available at ScienceDirect Immunology Letters journal homepage: www.elsevier.com/locate/immlet Review Guiding blind T cells and dendritic cells: A closer look at fibroblastic reticular cells found within lymph node T zones Sanjiv A. Luther, Tobias K. Vogt, Stefanie Siegert Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland article info Available online 17 February 2011 abstract It is within the T cell rich zone of secondary lymphoid organs (SLO) that dendritic cells (DC) present the captured pathogens to recirculating T cells in order to activate the rare antigen-specific T cells. While we have made considerable progress in understanding the biology of mobile hematopoietic cells found within SLO, notably DC and lymphocytes, we still have a lot to learn about the sessile stromal cells. This review is focused on the recent progress made in our understanding of the fibroblastic reticular stromal cells that form the ‘niches’ within the T zone. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Lymphocytes are generated within primary lymphoid tissues, namely the bone marrow (BM) and the thymus. Upon comple- tion of their maturation, these lymphocytes enter the blood stream and from then onward are constantly on the move between SLO, lymph and blood, thereby patrolling the body for infectious agents. SLO are specialized in filtering body fluids for infectious agents or ‘danger signals’ (‘antigens’), with the spleen filtering the blood, lymph nodes (LN) filtering the lymph and mucosal associated lym- phoid tissues such as Peyer’s Patches (PP) sampling antigens from mucosal surfaces. Experiments in mice lacking SLO have estab- lished that spleen, LN and PP are the only sites where adaptive immune responses are efficiently initiated [1,2]. A key feature of the SLO organization is the very distinct com- partmentalization into a B cell follicle (B zone or cortex), a T cell rich zone (T zone or paracortex) and medullary cords in LN and red pulp in spleen (Fig. 1). T and B lymphocytes enter the spleen through open-ended arteries in the red pulp or marginal zone before migrat- ing into the T or B zone of the white pulp, respectively. In contrast, lymphocytes enter the LN and PP from the blood by crossing high endothelial venules (HEV). Once inside the lymphoid tissue, B and T lymphocytes migrate into their respective zones, where they stay for several hours before leaving the tissue by entering the lymphatic vessels found in the medullary cords of LN or the venules found in the red pulp of the spleen [1–3]. 1.1. T zone microenvironment of secondary lymphoid organs It is within the T zone where recirculating T and B cells enter LN. While T cells reside within this zone for several hours, B cells E-mail address: sluther@unil.ch (S.A. Luther). quickly migrate into the adjacent B cell follicles. DC that have cap- tured antigen also migrate from the periphery via lymphatics or via blood into the T zone (Fig. 1). Therefore, the T zone is com- posed of many migratory cells, such as naive CD4+ and CD8+ T cells. In addition, it contains lymphatic endothelial cells (LEC) and blood endothelial cells (BEC). Particularly, HEV play a central role for lymphocyte recruitment. However, the T zone also contains some resident DC as well as a population of sessile stromal cells that form a dense network throughout that zone [1–3]. These stro- mal cells are an important architectural component of the T zone, but also contribute directly to lymphocyte recirculation and inter- action, as further summarized below. Despite the critical processes taking place within the T zone, our understanding of the resident cells defining this microenvironment is relatively poor. 1.2. General characteristics of stromal cells within lymphoid organs Lymphoid tissue stromal cells are found in primary and SLO and represent radiation-resistant, non-BM derived cells, including endothelial cells and fibroblasts [1–3]. The fibroblast-like cells are thought to be mainly of mesenchymal origin. They often associate with supporting collagen fibers that they produce. They form large networks and tightly connect with endothelial cells of lymphatics and blood vessels. Fibroblastic stromal cells in primary lymphoid organs and B cell follicles of SLO have been extensively studied and recognized not only as important architectural components of lym- phoid organs but as active organizers of their microenvironment by expressing cytokines, chemokines, prostanoids and adhesion molecules. BM stromal cells have been shown to play a critical role in B cell development, at least in part due to their role in promoting proliferation and differentiation of stem cells, includ- ing B cell precursors. Thymic stromal cells are critically involved in T cell proliferation and maturation, including positive selec- 0165-2478/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.imlet.2011.02.006