Summary Dendritic cells (DC) are rare, bone marrow-derived antigen-presenting cells that play a critical role in the induction and regulation of immune reactivity. In this article, we review the identification and characterization of liver DC, their ontogenic development, in vivo mobilization and population dynamics. In addition, we discuss the functions of DC isolated from liver tissue or celiac lymph, or propagated in vitro from liver-resident haemopoietic stem/progenitor cells. Evidence concerning the role of DC in viral hepatitis, liver tumours, autoimmune liver diseases, granulomatous inflammation and the outcome of liver transplantation is also discussed.Key words: dendritic cells, immunity, liver, liver disease, tolerance.
Identification of hepatic dendritic cells in situIn both rodents and humans, immunohistochemical staining of normal adult livers identifies major histocompatibility complex (MHC) class II + , presumptive dendritic cells (DC) primarily in portal areas, with a few cells scattered throughout the parenchyma. 1-7 The constitutive expression of MHC II antigens (Ag) by these cells, and their dendriform morphology, led to their initial classification as DC. Although MHC class II Ag are also expressed constitutively by human, 7 but not rodent liver macrophages (Kupffer cells), 3 the restricted distribution of DC allows these cells to be readily distinguished from Kupffer cells, which are evident throughout the parenchyma. 1,2,4 MHC class II + presumptive DC have also been described in the liver capsule. 7 In addition to differences in microanatomic location and surface immunophenotype, liver DC and Kupffer cells are distinguished by the absence of non-specific esterase and α-napthylacetate esterase activity in the former cell type. 1,8
Characterization of hepatic dendritic cells in situFew reports have detailed the location of cells immunoreactive with monoclonal Ab (mAb) recognizing DC-associated Ag within the liver. In rats, MHC class II + and/or OX62 + cells are found predominantly in portal areas, with a few positive cells in the sinusoids and around the central vein. 9-11 Immunostaining for ED1 (monocytes/macrophages), ED2 (macrophages/Kupffer cells) and OX6, identifies two distinct phenotypes of hepatic DC: (i) ED1 + ED2 -OX6 + and (ii) ED1 -ED2 -OX6 + . 10 Interestingly, rat hepatic MHC class II + DC appear to express variable levels of CD4, 3,12 which is common in DC in other peripheral tissues of this species. 3,13,14 Mouse CD11c +4 and CD205 + cells 15 are mainly located periportally, as reported for MHC II + cells. The in situ phenotype of human liver DC has been examined quite extensively. 7 Interstitial DC in normal mouse liver exhibit an 'immature' or 'Ag-processing' phenotype, as described for DC in other non-lymphoid tissues. Immunohistochemical staining of normal mouse liver for the costimulatory molecules CD40, CD80 and CD86 16,17 indicates that normal liver DC do not constitutively express detectable amounts of these molecules in situ; a phenotype characteristic of DC in other...