Structure and Immune Function of Afferent Lymphatics and Their Mechanistic Contribution to Dendritic Cell and T Cell Trafficking

Afferent lymphatic vessels (LVs) mediate the transport of antigen and leukocytes to draining lymph nodes (dLNs), thereby serving as immunologic communication highways between peripheral tissues and LNs. The main cell types migrating via this route are antigen-presenting dendritic cells (DCs) and antigen-experienced T cells. While DC migration is important for maintenance of tolerance and for induction of protective immunity, T cell migration through afferent LVs contributes to immune surveillance. In recent years, great progress has been made in elucidating the mechanisms of lymphatic migration. Specifically, time-lapse imaging has revealed that, upon entry into capillaries, both DCs and T cells are not simply flushed away with the lymph flow, but actively crawl and patrol and even interact with each other in this compartment. Detachment and passive transport to the dLN only takes place once the cells have reached the downstream, contracting collecting vessel segments. In this review, we describe how the anatomy of the lymphatic network supports leukocyte trafficking and provide updated knowledge regarding the cellular and molecular mechanisms responsible for lymphatic migration of DCs and T cells. In addition, we discuss the relevance of DC and T cell migration through afferent LVs and its presumed implications on immunity.