Prenodal lymph is generated from the interstitial fluid that surrounds organs, and thus contains products of organ metabolism and catabolism. New proteomic analyses have identified in lymph proteins and peptides that are derived from capillary extravasation and tissue-specific proteins. Many of these peptides are detected at nanomolar concentrations in the lymph prior to passage through a regional lymph node. Before entering the node and once inside proteins and processed peptides are filtered from the lymph by circulating immature DC or non-activated nodal APC (macrophages, B cells and immature DC). Here, we suggest that this process ensures organspecific self-antigens are displayed to circulating and nodal antigen-presenting cells, thus contributing to the maintenance of peripheral tolerance.
The lymphatic system: a historical perspectiveHistorically, the first mention of the lymphatic system is found in a medical treaty written by the Greek physician Hippocrates in the V century B.C. whereas Galen (II century A.D.) reported the first dissection of the mesenteric lymph nodes. It was not until the seventeenth century that the lymphatic vessels were described as a separate system that carry aqueous fluid distinct from the blood. Until the early 1900s it was thought that the lymph was a cellfree, protein-free ultrafiltrate of the plasma composed only of electrolytes. In 1925 it was discovered that the prenodal lymph has a cellular component and contains high levels of lipids and proteins [1]. Even though it is generally regarded that the analysis of the pre-nodal lymph could provide a molecular signature of organ-specific "omics" (proteomic, lipidomic and metabolomic) transported to the regional lymph node, the difficulty in collecting primary material has hampered a broader development of the field [2]. Recently, a few studies have been performed on human bovine and goat lymph, collected at different sites, which have provided the first glimpse into the composition of the lymphatic fluid.In this review we will focus on current knowledge of the proteomic and peptidomic composition of the lymph under physiological conditions, with particular emphasis on its