The role of NKT cells in animal models of autoimmune hepatitis

NKT cells expressing invariant T-cell receptors are an abundant cell population in the mouse liver, and much evidence has been accumulating which shows that they play an important role in immune responses in this organ. In this review, the putative function of NKT cells in autoimmune hepatitis is discussed based on results from various mouse models. Features and functions of invariant NKT cells are summarized to set the stage to explain how these cells induce liver injury following the injection of mitogen concanavalin A or NKT-cell receptor ligand alpha-GalCer. Results are discussed which show that alcohol consumption can aggravate liver injury by NKT cells, whereas expression of a hepatitis C virus protein in hepatocytes can protect against injury. Hepatocytes, therefore, can modulate sensitivity to NKT-cell-mediated attack. Moreover, experiments that elucidate how NKT cells induce liver injury and how they are regulated to perform this function are discussed. Specific attention is given to the recently discovered role of purinergic receptor P2X(7) in regulating NKT cells. The conclusion is drawn that the P2X(7) receptor constitutes a sensor that senses purine-based danger signals, which trigger mechanisms that cause inhibition or stimulation of NKT-cell functions.