A critical role for dendritic cells in the formation of lymphatic vessels within tertiary lymphoid structures

Ectopic, or tertiary, lymphoid aggregates often form in chronically inflamed areas. Lymphatic vessels, as well as high endothelial venules, form within these lymphoid aggregates, but the mechanisms underlying their development are poorly understood. Overexpression of the chemokine CCL21 in the thyroid of transgenic mice leads to formation of lymphoid aggregates containing topologically segregated T and B lymphocytes, dendritic cells (DCs), and specialized vasculature, including Lyve-1(+)/Prox-1(+) lymphatic vessels. In this article, we show that adoptive transfer of mature CD4(+) T cells into animals expressing CCL21 in a RAG-deficient background promotes the influx of host NK cells and DCs into the thyroid and the formation of new lymphatic vessels within 10 d. This process is dependent on the expression of lymphotoxin ligands by host cells, but not by the transferred CD4(+) T cells. Ablation of host DCs, but not NK cells, reduces the formation of new lymphatic vessels in the thyroid. Taken together, these data suggest a critical role for CD11c(+) DCs in the induction of lymphangiogenesis in tertiary lymphoid structures.