Pathogenesis of post-thymectomy autoimmune gastritis. Identification of anti-H/K adenosine triphosphatase-reactive T cells.
Autoimmune gastritis spontaneously develops following thymectomy of 3-day-old BALB/c mice (d3Tx). These mice develop autoantibodies to the gastric parietal cell proton pump, H/K ATPase, and aberrant expression of the H/K ATPase in the neonatal thymus prevents the induction of disease post-thymectomy. To characterize the effector cells mediating autoimmune gastritis, we isolated H/K ATPase-enriched preparations of parietal cell microsomes and further purified the enzyme by lectin affinity chromatography. Both preparations induced significant proliferative responses of gastric lymph node cells, which were mediated by CD4+, MHC class II-restricted T cells. Surprisingly, T cells reactive to the Ag could only be demonstrated in lymph nodes in the immediate proximity of the stomach; little or no response was seen when mesenteric or peripheral lymph nodes were tested. It is likely that the H/K ATPase-reactive T cells are actually the effector cells in this disease, as they could only be detected in mice that developed gastritis, as indicated by anti-parietal cell Ab, gastric inflammation, and the presence of cells capable of transferring disease into nu/nu mice. H/K ATPase-specific T cell proliferative responses could first be detected 5 wk post-thymectomy and were accompanied by high background responses at this time point. These latter responses may represent enhanced syngeneic MLRs, which we have previously shown to be elevated in d3Tx mice. Characterizations of the H/K ATPase-reactive and self-reactive T cell populations may reveal the factors that break peripheral T cell tolerance and lead to the development of organ-specific autoimmune disease.
Suri-Payer
E
E
Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kehn
P J
PJ
Cheever
A W
AW
Shevach
E M
EM
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005756:Gastritis / Q000209:etiology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008861:Microsomes / Q000201:enzymology; D010295:Parietal Cells, Gastric / Q000201:enzymology* / Q000276:immunology; D011817:Rabbits; D013934:Thymectomy / Q000009:adverse effects*
D001324:Autoantigens; D017506:H(+)-K(+)-Exchanging ATPase