Why lymph nodes grow

At the initiation of an immune response, lymph nodes can double in size in a day and can be ten times their original size in five to seven days. Webster and colleagues report on page 1903 that dendritic cells, quite distinct from their function in antigen presentation, stimulate endothelial cell proliferation and vascular growth in the growing lymph node. Peripheral challenge (such as immunization) induces dendritic cells to mature and migrate to the lymph nodes. But what is their role once there? Dendritic cells are well known for their role in B and T cell lym-phocyte stimulation but, surprisingly, Lu's team found that without lym-phocytes (in Rag −/− mice) dendritic cells could activate lymph node growth and endothelial cell proliferation almost as effectively. Vascular endothelial growth factor (VEGF) has been implicated in lymph node growth, and the team found that dendritic cells could increase VEGF levels in the lymph node, again, without the need for lymphocytes. Increased VEGF and increased endothelial cell proliferation required dendritic cell–mediated recruitment of cells from the circulation. Either these recruited cells or other lymph node cells (but not the dendritic cells) are then thought to produce the VEGF. Determining how VEGF levels are up-regulated is the subject of ongoing study. Enlargement of the lymph nodes is a normal step in combating infection, but it also occurs during autoimmune responses. One possibility for combating lymph node growth during autoimmu-nity is antiangiogenic drugs, which were developed to combat tumors. If immune cells are an army, then a graft transplant is a foreign invasion. New work by Yu et al. on page 1851 shows that antigen-presenting cells (APCs) from the graft are rapidly killed by the host's first line of defense: natural killer (NK) cells. But far from hindering the chance of graft survival, this battle actually improves it. NK cells are known to improve the chance of graft survival, but how they do this was unknown. Li's team wanted to know what happens to graft APCs when NK cells are absent. Using mice that lacked a full-blown rejection response (because they lacked lympho-cytes), the team were able to follow the fate of donor APCs for longer than would normally be possible. They found that in the absence of NK cells, donor APCs could roam free in the host, as confirmed by their presence in spleen, liver, and lung. In the presence of NK cells, however, injected or …