Having it all? Stem cells, haematopoiesis and lymphopoiesis in adult human liver

Because of its location and function, the liver is continuously exposed to large antigenic loads that include pathogens, toxins and tumour cells, as well as harmless dietary and commensal proteins and peptides. Therefore, the liver must be actively immunocompetent and, at the same time, control inappropriate inflammatory responses to dietary and other harmless antigens encountered in the portal circulation. In addition to conventional CD4(+) and CD8(+) T lymphocytes from the circulation, several specialized lymphoid populations are found in the liver to meet these diverse immunological challenges. These populations display the functional and phenotypic proper-ties of innate cells as well as conventional CD4(+) or CD8(+) helper and cytotoxic T lymphocytes and B cells. The innate lymphoid cells include gammadeltaTCR(+) T cells, B1-B cells and NKT cells as well as large numbers of NK cells. The origin of these cells is unknown, but their murine counterparts have been shown to be capable of differentiation in situ in adult liver. Because haematopoietic stem cells have been found in adult human liver as well as molecular evidence of T-cell maturation, we hypothesize that some resident human hepatic lymphoid cells, particularly those expressing innate phenotypes, also differentiate locally. In particular, it is likely that the adult human liver is an important site of NK cell maturation. In this review, we explore the evidence for an active lymphopoietic role for the normal adult human liver.