Lymph Node Cortex

Abstract: The lymph node cortex is a critical site for encounter between recirculating T cells and their specific antigens. Due to its extreme plasticity, little is understood of the underlying functional unit of the lymph node cortex, the paracortical cord. The idealized paracortical cord (approximately 100 microns by 1000 microns) stretches from a medullary cord to the base of a B-cell follicle. In cross-section, a cord can be visualized as a set of nested cylinders consisting of spaces bounded by cells. The spaces are: i) the lumen of the high endothelial venule (HEV), ii) perivenular channels-narrow potential spaces (0.1 micron) tightly encircling the HEV, iii) corridors-broad spaces (10-15 microns) constituting the majority of the parenchyma, and iv) the cortical sinus. In addition to these spaces for cell traffic, the conduit (fifth space) is a special delivery system for the transit of soluble factors to the HEV and emigrating lymphocytes. The cellular barriers between these spaces are high endothelium, fibroblastic reticular cells, or sinus-lining cells. This review describes the spaces of the paracortical cord and their cellular boundaries, outlines the movement of cells and fluids through these spaces, and discusses how this anatomy affects the efficiency of surveillance by T cells.

Abstract: After host entry through mucosal surfaces, human immunodeficiency virus-1 (HIV-1) disseminates to lymphoid tissues to establish a generalized infection of the immune system. The mechanisms by which this virus spreads among permissive target cells locally during the early stages of transmission and systemically during subsequent dissemination are not known. In vitro studies suggest that the formation of virological synapses during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer. It is unclear, however, whether T-cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial and lymphoid tissues. Here, using multiphoton intravital microscopy, we examine the dynamic behaviour of HIV-infected T cells in the lymph nodes of humanized mice. We find that most productively infected T cells migrate robustly, resulting in their even distribution throughout the lymph node cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope-dependent cell fusion. Both uncoordinated motility of syncytia and adhesion to CD4(+) lymph node cells led to the formation of long membrane tethers, increasing cell lengths to up to ten times that of migrating uninfected T cells. Blocking the egress of migratory T cells from the lymph nodes into efferent lymph vessels, and thus interrupting T-cell recirculation, limited HIV dissemination and strongly reduced plasma viraemia. Thus, we have found that HIV-infected T cells are motile, form syncytia and establish tethering interactions that may facilitate cell-to-cell transmission through virological synapses. Migration of T cells in lymph nodes therefore spreads infection locally, whereas their recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection.

Abstract: Thymidine-H3 was injected into the femoral and tibial marrow (labeled marrow) of guinea pigs while the hind limb circulation was arrested temporarily and non-radioactive thymidine was administered systemically. Blood and lymphoid tissue radioautographs were subsequently examined for the presence of marrow-derived labeled cells. Small lymphocytes in the labeled marrow showed a wave of labeling, maximal at two to three days. Concurrently, labeled small lymphocytes appeared in the blood and lymphoid tissues, mainly the spleen and mesenteric lymph node. Their numbers were greatest at four to five days, and declined rapidly thereafter. At first they appeared predominantly in the splenic red pulp and throughout the lymph node cortex, including the subcapsular sinus. By four to five days they were also concentrated in the splenic white pulp, including periarteriolar lymphoid sheaths, and in the lymph node medullary cords. They were detected within medullary sinuses, hilar lymphatics and thoracic duct lymph. Labeled monocytes and large lymphoid cells also appeared in the blood and lymphoid tissues, mainly in the spleen. It is concluded that bone marrow is a major source of circulating newly-formed small lymphocytes many of which migrate rapidly into the spleen and mesenteric lymph node.

Abstract: A method is described whereby antisera raised in rabbits to rat thoracic duct lymphocytes were made specific for the plasma membrane antigens of T and B lymphocytes. These lymphocyte-specific antisera were used in immunofluorescence assays to study the distribution of B and T cells in lymphocyte containing tissues and body fluids of the rat. Rabbit antirat B-cell serum (ALSB) reacted selectively with the surfaces of lymphocytes in the lymphoid follicles of lymph node cortex and in the follicles and marginal zones of splenic white pulp, but not with the surfaces of germinal center cells or plasma cells. An identical pattern of fluorescent staining was obtained with rabbit antirat Ig serum. It was shown by blocking, absorption, and immunoprecipitation studies that ALSB was composed in large part of antibodies to rat Ig, but that it contained antibodies to other B-cell antigens as well. Rabbit antirat T-cell serum (ALST) reacted selectively with the surfaces of lymphocytes in the paracortex of lymph node and in the periarteriolar sheath of spleen, and with thymocytes. ALST did not display anti-Ig activity. ALST reacted with approximately 100% thymocytes and with 90% thoracic duct, 80% lymph node, 60% blood, 50% spleen, and 10% bone marrow lymphocytes in suspensions of cells from these sources. ALSB reacted with the remainder of the lymphocytes in the suspensions, except for bone marrow in which only 59% of lymphocytes had detectable B- or T-cell surface antigens. The population of T lymphocytes in rat bone marrow was depleted by drainage of lymphocytes from a thoracic duct fistula, thereby establishing their membership in the pool of recirculating T cells. Approximately 14% of lymphocytes issuing from the thoracic duct of TxBM donors reacted with ALST. The presence in these animals of a small number of T cells, calculated to be approximately 2% of the normal value, may account for the limited capacity of TxBM rats to respond to antigens that induce a cell-mediated immune response.