between the ages of 10 and 20 and 45 and 70 years and has To determine the clinical, biochemical, and histologia relatively benign course at least in adults, 3 whereas LKMcal features, and outcome of childhood autoimmune 1 positive patients have a more severe disease with progreshepatitis (AIH), we reviewed the medical records of 52 sion to cirrhosis despite immunosuppressive treatment. gest that ANA/SMA positive AIH has two peaks of incidence median age: 10.5, range 2.3-14.9 years). At presentation, four children were positive for ANA alone (titer range: 1:80-1:320), 10 for SMA alone (titer range: 1:40-1:2560) and 14 for both ANA (titer range: 1:20-1:5120) and SMA (titer range: 1:40-1:1280). In two paAbbreviations: AIH, autoimmune hepatitis; ANA/SMA, nuclear and/or smooth muscle

Because of its location and function, the liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and harmless dietary antigens. The range of local immune mechanisms required to cope with this diverse immunological challenge is now being appreciated. The liver has an "epithelial constitution" and contains large numbers of phagocytic cells, antigen-presenting cells and lymphocytes and is a site for the production of cytokines, complement components and acute phase proteins. In this review, we focus on the hepatic lymphoid system, which is currently emerging as an important arm of the immune system in the liver for targeting pathogens as well as for the recognition of cells that are modified as a result of infection or tumor transformation. We show that this organ contains a heterogeneity of lymphoid cells with diverse recognition mechanisms and functions. There are conventional T lymphocytes that use clonotypic receptors to identify and respond to antigenic peptides presented in the context of polymorphic class I and class II major histocompatibilty complex (MHC) molecules. But these cells are outnumbered by lymphoid cells that recognize common structures using receptors with limited diversity. These mediators of innate immunity against infectious pathogens and malignant cells respond immediately to stimuli and function as a temporal (and perhaps evolutionary) bridge for the adaptive immune response.

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Invariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond rapidly by killing tumor cells and release cytokines that activate and regulate adaptive immune responses. They are essential for tumor rejection in various mouse models, but clinical trials in humans involving iNKT cells have been less successful, partly due to their rarity in humans compared with mice. Here we describe an accumulation of functional iNKT cells in human omentum, a migratory organ with healing properties. Analysis of 39 omental samples revealed that T cells are the predominant lymphoid cell type and of these, 10% expressed the invariant Va24Ja18 TCR chain, found on iNKT cells, higher than in any other human organ tested to date. About 15% of omental hematopoietic cells expressed CD1d, compared with 1% in blood (po0.001). Enriched omental iNKT cells killed CD1d + targets and released IFN-c and IL-4 upon activation. Omental iNKT-cell frequencies were lower in patients with severe obesity (p 5 0.005), and with colorectal carcinoma (p 5 0.004) compared with lean healthy subjects. These data suggest a novel role for the omentum in immune regulation and tumor immunity and identify it as a potential source of iNKT cells for therapeutic use.