The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses

The Liver remains a hematopoietic organ after birth and can produce all leu kocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipo polysaccharide (LPS) and bacterial superantigens, and produce interleukin ( IL)-12. IL-12 and other monokines (IL-18 etc.) produced by Kupffer cells ac tivate liver natural killer (NK) cells and NK1.1 Ag+T cells to produce inte rferon-gamma and thereby acquire cytotoxicity against tumors and microbe-in fected cells. These liver leukocytes and the T helper 1 immune responses in duced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this d efense system is inadequately activated, shock associated with multiple org an failure takes place. Activated liver NK1.1 Ag+T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ Teens and another T-cell subset with an intermediate T-cell receptor, CD 122(+)CD8(+) T cells, can develop independ ently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells phys iologically develop in situ from their precursors, presumably due to bacter ial antigens brought from the intestine via the portal vein. NK cells activ ated by bacterial superantigens or LPS are also probably involved in the va scular endothelial injury in Kawasaki disease.