Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm

The circulatory and migratory properties of white blood cells have evolved to allow efficient surveillance of tissues for infectious pathogens and rapid accu­ mulation at sites of injury and infection. Lymphocytes continually patrol the body for foreign antigen by recirculating from blood, through tissue, into lymph, and back to blood. Lymphocytes acquire a predilection, based on the environment in which they first encounter foreign antigen, to home to or recirculate through that same environment (39, 40). Granulocytes and mono­ cytes cannot recirculate, but emigrate from the bloodstream in response to molecular changes on the surface of blood vessels that signal injury or infec­ tion. Lymphocytes can similarly accumulate in response to inflammatory stim­ uli. The nature of the inflammatory stimulus determines whether lymphocytes. monocytes, neutrophils, or eosinophils predominate, and thus exercises spec­ ificity in the molecular signals or "area codes" that are displayed on endothe­ lium and control traffic of particular leukocyte classes. Recent findings show that the "traffic signals" for lymphocyte recirculation and for neutrophil and monocyte localization in inflammation are strikingly similar at the molecular level. These traffic signal or area code molecules are

Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration

Selectins and their ligands: current concepts and controversies.

Lymph nodes (LNs) are the organs where innate immune responses lead to acquired immunity, where some of our most devastating pathogens evade immunity, and where autoreactive lymphocytes first encounter tissue-specific self-antigens and are either tolerized or activated. The many roles of LNs depend on the coordinated migration of its cellular constituents. This article covers new insights into the organization and microvascular specialization of LNs, the guidance mechanisms that allow lymphocytes and antigen-presenting cells to find their correct place in the nodal parenchyma; and the role of afferent lymph flow in LN function.

Homing and cellular traffic in lymph nodes

Lymphangiogenesis: Molecular Mechanisms and Future Promise

Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC-145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis.

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P R Streeter

Papers

The influence of afferent lymphatic vessel interruption on vascular addressin expression.