Regulation by chemokines of circulating dendritic cell precursors, and theformation of portal tract-associated lymphoid tissue, in a granulomatous liver disease

We have studied the recruitment and roles of distinct dendritic cell (DC) p recursors from the circulation into Propionibacterium acnes-induced granulo mas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and m atured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associat ed lymphoid tissue" (PALT). Macrophage inflammatory protein 1 alpha attract ed blood DC precursors to the sinusoidal granuloma, whereas secondary lymph oid organ chemokine (SLC) attracted mature DCs to the newly identified PALS . Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid or gan like liver, and participate in the granulomatous reaction in response t o specific chemokines.