Immunopathology of autoimmune gastritis: lessons from mouse models.

| Immunopathology of autoimmune gastritis: Lessons from mouse models F. Alderuccio and B.H. Toh Department of Pathology and Immunology, Monash University Medical School, Commercial Road, Prahran, Victoria, Australia Offprint requests to: Dr. Frank Alderuccio, Department of Pathology and Immunology, Monash University Medical School, Commercial Road, Prahran, Victoria, 3181 Australia. e-mail: [email protected] Summary. Autoimmune gastritis in humans is a chronic inflammatory disease of the stomach accompanied by specific destruction of gastric parietal and zymogenic cells resulting in pernicious anemia. Human gastritis can be accurately reproduced in mice and is characterised by autoantibodies to the a- and ß-subunits of the gastric H/K ATPase (the enzyme responsible for gastric acid secretion) and cellular destruction of parietal and zymogenic cells within the gastric gland. Studies with these mouse models have given us our current concepts of the immunopathogenesis of the gastritis. Mouse models have shown that a T cell response is generated to the a- and ß-subunits of the H/K ATPase and that an immune response to the ß-subunit seems to be required for disease initiation. Using these models, we have defined key events associated with a damaging autoimmune response to the gastric H/K ATPase. The mechanisms associated with the cellular destruction associated with autoimmune gastritis are not know, but may involve signaling through death inducing pathways such as the Fas/FasL and TNF/TNFR pathways. This knowledge should permit us to develop strategies to prevent and treat the gastritis. Histol. Histopathol. 15, 869-879 (2000) Key words: Autoimmune gastritis, Autoimmunity, Transgenic mice |