Cutting edge:: Nonproliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis

Ectopic formation of secondary lymphoid tissue is initiated by the local attraction of naive T and B cells. In this study, we describe a novel type of organized lymphoid structure in the lung of human idiopathic pulmonary fibrosis, with key features of lymphoid neogenesis, including: 1) recently activated CD40 ligand (CD40L)(+) T cells; 2) variable numbers of activated CD40(+)/CD40L(+) B cells, sometimes organized injollicles; 3)fully mature dendritic cells (DC) expressing CD40, CD83, CD86, and DC-lysosome-associated membraneprotein; 4) the expression of the chemokine CCL21; 5) the presence of vessels with characteristics of high endothelial venules; and 6) a dense network of follicular DC. Surprisingly, these structures are devoid of CCR7(+) naive T cells, proliferating lymphocytes, andgerminal centers, suggesting that newly recruited activated DC and Ag-experienced lymphocytes can drive lymphoid neogenesis and that factors present within the lymphoid aggregates, such as CD40L, are essential to induce DC maturation.