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The lymphatic system is important in mounting an immune response to foreign antigens and tumors in humans and animal models. The liver produces a large amount of lymph, and its lymphatic system is divided into three major components: the portal, sublobular and superficial lymphatic vessels. Despite the fact that mice are the most commonly used laboratory animals, detailed descriptions of the anatomical location and function of the lymph nodes (LNs) that drain the liver are surprisingly absent. In this study, we found that the portal and celiac LNs adjacent to mouse liver were stained with Evans blue within 5-8 min. Enhanced green fluorescence protein (EGFP)-positive cells from the liver also drained into the two aforementioned LNs. These data indicate that the portal and celiac LNs drain the mouse liver. Lymphadenectomy of the identified liver-draining LNs resulted in hepatitis B virus (HBV) persistence in immunocompetent mice compared with the sham group. In addition, the frequencies of CD8(+) T cells and dendritic cells (DCs) increased significantly in the liver-draining LNs after hydrodynamic injection of HBV plasmid. Liver-draining LN cells in HBV plasmid-injected mice also showed significant antigen-specific proliferation in response to stimulation with recombinant hepatitis B core antigen in vitro. Adoptive transfer of these cells into Rag1(-/-) mice induced a reduction in the serum concentration of hepatitis B surface antigen (HBsAg) compared to liver-draining LN cells in uninjected mice. Altogether our data characterize the liver-draining LNs and provide evidence that the liver-draining LNs induce an anti-HBV-specific immune response responsible for HBV clearance.

Characterization of the liver-draining lymph nodes in mice and their role in mounting regional immunity to HBV