The physiology of lymphocyte migration through the single lymph node in vivo

Lymphocytes are mobile cells, continually recirculating between the blood and the tissues via the lymph. In order to maintain immune surveillance, the majority of lymphocyte traffic occurs through lymph nodes in vivo. Although a great deal of work has been done to elucidate the molecular mechanisms whereby lymphocytes leave the blood and enter the lymph node, lymphocyte traffic also requires that the lymphocyte successfully transit extravascular tissue and enter the lymph following transendothelial migration. The regulation of cell movement through lymph nodes, specific cellular positioning within the nodes, and eventual entry into the efferent lymphatics are poorly understood. The process of lymphocyte recirculation occurs in a physiological background, and in vivo systems have been particularly useful in uncovering the nuances of the process. This review summarizes available data about the recirculation of lymphocytes through the lymph node and the interaction of recirculating lymphocyte pools in vivo. The importance of factors in afferent lymph, the specific distribution of extracellular matrix proteins, potential soluble regulators of cell traffic, and evidence for an active role of lymphatic endothelial cells in the regulation of lymphocyte traffic are discussed. It seems likely that future work will need to be directed at determining the relative importance of these post-transendothelial migration regulators of lymphocyte traffic.