Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes.

T-cell immunity in the liver is tightly regulated to prevent chronic liver inflammation in response to antigens and toxins derived from food and intestinal bacterial flora. Since the main sites of T cell activation in response to foreign components entering solid tissues are the draining lymph nodes (LN), we aimed to study whether Antigen-Presenting Cell (APC) subsets in human liver lymph-draining LN show features that may contribute to the immunologically tolerant liver environment. Healthy liver LN, iliac LN, spleen and liver perfusates were obtained from multi-organ donors, while diseased liver LN were collected from explanted patient livers.

Migration of allosensitizing donor myeloid dendritic cells into recipients after liver transplantation.

It is thought, but there is no evidence, that myeloid dendritic cells (MDCs) of donor origin migrate into the recipient after clinical organ transplantation and sensitize the recipient's immune system by the direct presentation of donor allo-antigens. Here we show prominent MDC chimerism in the recipient's circulation early after clinical liver transplantation (LTx) but not after renal transplantation (RTx). MDCs that detach from human liver grafts produce large amounts of pro-inflammatory [tumor necrosis factor alpha and interleukin 6 (IL-6)] and anti-inflammatory (IL-10) cytokines upon activation with various stimuli, express higher levels of toll-like receptor 4 than blood or splenic MDCs, and are sensitive to stimulation with a physiological concentration of lipopolysaccharide (LPS).

Dexamethasone transforms lipopolysaccharide-stimulated human blood myeloid dendritic cells into myeloid dendritic cells that prime interleukin-10 production in T cells.

Myeloid dendritic cells (MDC) play an important role in antigen-specific immunity and tolerance. In transplantation setting donor-derived MDC are a promising tool to realize donor-specific tolerance. Current protocols enable generation of tolerogenic donor MDC from human monocytes during 1-week cultures.

Allosuppressive donor CD4+CD25+ regulatory T cells detach from the graft and circulate in recipients after liver transplantation.

Organ transplantation (Tx) results in a transfer of donor leukocytes from the graft to the recipient, which can lead to chimerism and may promote tolerance. It remains unclear whether this tolerance involves donor-derived regulatory T cells (Tregs). In this study, we examined the presence and allosuppressive activity of CD4+CD25+Foxp3+ Tregs in perfusates of human liver grafts and monitored the cells presence in the circulation of recipients after liver Tx.

Characterization of human liver dendritic cells in liver grafts and perfusates.

It is generally accepted that donor myeloid dendritic cells (MDC) are the main instigators of acute rejection after organ transplantation. The aim of the present study was to characterize MDC in human donor livers using liver grafts and perfusates as a source. Perfusates were collected during ex vivo vascular perfusion of liver grafts pretransplantation.