Requirements for autoimmune responses to mouse gastric autoantigens.
Autoimmune gastritis, in which the H+/K(+)-ATPase of parietal cells is the major antigen, is one of the most common autoimmune diseases. Here we examined if specific properties of the H+/K(+)-ATPase or parietal cells are involved in rendering them autoimmune targets. The model antigens beta-galactosidase and ovalbumin (OVA) were expressed in parietal cells of transgenic mice. On experimental induction of autoimmune gastritis by neonatal thymectomy, autoantibodies to beta-galactosidase developed in mice expressing beta-galactosidase in parietal cells, a response that was independent of either the response to the gastric H+/K(+)-ATPase or gastric inflammation. In contrast, mice that expressed OVA in parietal cells did not exhibit an antibody response to OVA after thymectomy. However, increasing the frequency of anti-OVA T lymphocytes in OVA-expressing mice resulted in autoantibodies to OVA and gastritis. These studies indicate that parietal cells can present a variety of antigens to the immune system. Factors such as the identity and expression level of the autoantigen and the frequency of autoreactive T cells play a role in determining the prevalence and outcome of the particular immune response. In addition, as not all mice of a particular genotype displayed autoimmunity, random events are involved in determining the target of autoimmune recognition.
Scarff
K L
KL
Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Melbourne, Victoria, Australia.
Judd
L M
LM
Wilson
W E
WE
Laurie
K L
KL
Toh
B H
BH
Gleeson
P A
PA
van Driel
I R
IR
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D005260:Female; D005756:Gastritis / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000276:immunology; D013270:Stomach / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
D001324:Autoantigens; D007074:Immunoglobulin G; D010047:Ovalbumin; D001616:beta-Galactosidase; D017506:H(+)-K(+)-Exchanging ATPase