Liver Dendritic Cells Are Less Immunogenic Than Spleen Dendritic Cells because of Differences in Subtype Composition

Abstract

The unique immunological properties of the liver may be due to the function of hepatic dendritic cells (DC). However, liver DC have not been well characterized because of the difficulty in isolating adequate numbers of cells for analysis. Using immunomagnetic bead and flow cytometric cell sorting, we compared freshly isolated murine liver and spleen CD11c+ DC. We found that liver DC are less mature, capture less Ag, and induce less T cell stimulation than spleen DC. Nevertheless, liver DC were able to generate high levels of IL-12 in response to CpG stimulation. We identified four distinct subtypes of liver DC based on the widely used DC subset markers CD8α and CD11b. Lymphoid (CD8α+CD11b−) and myeloid (CD8α−CD11b+) liver DC activated T cells to a similar degree as did their splenic DC counterparts but comprised only 20% of all liver DC. In contrast, the two more prevalent liver DC subsets were only weakly immunostimulatory. Plasmacytoid DC (B220+) accounted for 19% of liver DC, but only 5% of spleen DC. Our findings support the widely held notion that liver DC are generally weak activators of immunity, although they are capable of producing inflammatory cytokines, and certain subtypes potently activate T cells.

Dissecting the dendritic cell controversy in chronic hepatitis B virus infection

“…55 DCs in the mouse liver produce more IL-10 and display reduced T-cell stimulatory capacity compared with splenic DCs. 56,57 The little information that is known about human intrahepatic DC function corroborates these general observations. 58,59 Despite the challenges of accessing specimens and extracting cells, a better understanding of how DCs and monocytes function in the intrahepatic environment is important for therapeutic development.…”

Organ-derived dendritic cells have differential effects on alloreactive T cells

“…43 This can be attributed in part to its dendritic cells, 44,45 and possibly to the CD8 Ϫ CD11b Ϫ dendritic cell subset. 46 We here extend the latter report, which described less maturity and allostimulatory capacity of liver-derived dendritic cells in a Th2-driven BALB/c into C57BL/6 model, now to a Th1-driven B10.BR into C57BL/6 model. These results may have been biased due to a lack of sensitivity of hepatic dendritic cells to LPS.…”

Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion

“…That the depletion of DCs has no effect on the responsiveness of liver NK T cells is not surprising in light of a recent study showing that liver DCs are far less immunogenic and far fewer in number than those found in the spleen (34). Because DCs do not seem to be important in hepatic NK T cell antigen presentation, we considered Kupffer cells as an alternative cell type that might act as APCs for liver NK T cells.…”