Autoimmune chronic liver disease as a model of human autoimmunity

Although clonal deletion and clonal energy have been demonstrated in transgenic mice, the findings that autoreactive B or T cells are present in healthy subjects suggest that they are not the sole mechanisms of tolerance. As regards helper T lymphocytes, tolerance to self-antigens can arise by preventing class II MHC expression on non-lymphoid cells and autoantigen presentation to helper T cells initiating the autoimmune response. Autoimmune chronic active hepatitis (CAH) seems to be a good model of self-tolerance bypass. Hepatocytes are able to express class II molecules and can perform accessory cell functions with respect to T cell clones generated from lymphocytes infiltrating the liver in autoimmune CAH patients. The class II antigen expression on hepatocytes may be modulated by IFN-gamma released by infiltrating T lymphocytes; thus, the activated liver cells can present autoantigens to autoreactive T cell clones. On the other hand, these findings may occur only when the upregulation of IFN-gamma or other lymphokines permits the expression of rare class II antigens on hepatocytes capable of binding particular residues of a liver-autoantigen which are recognized by specific autoreactive T cell clones binding different residues on the same epitope.