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.
Barnaba
V
V
Istituto I Clinica Medica, Università La Sapienza, Rome, Italy.
Franco
A
A
Balsano
F
F
D001327:Autoimmune Diseases / Q000209:etiology*; D015551:Autoimmunity; D006681:HLA-D Antigens; D006521:Hepatitis, Chronic / Q000209:etiology*; D006801:Humans; D008222:Lymphokines / Q000276:immunology; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology
D006681:HLA-D Antigens; D008222:Lymphokines