Abstract
Autoimmune gastritis induced by neonatal thymectomy of mice is a CD4^+^ T cell‐mediated organ‐specific autoimmune disease. The characteristic features of autoimmune gastritis, which include a mononuclear infiltrate within the gastric mucosa, loss of parietal and chief cells and circulating autoantibodies to the gastric H^+^/K^+^ ATPase, appear 6–10 weeks after thymectomy. Here we have assessed the role of interferon‐γ (IFN‐γ) in the pathogenesis of the gastric lesion. Splenic T cells derived from mice with gastritis produced three‐ to tenfold more IFN‐γ than T cells from normal animals after stimulation with anti‐CD3 antibodies. Treatment of neonatally thymectomized mice at weekly intervals for 6 or 12 weeks with a neutralizing rat monoclonal antibody to mouse IFN‐γ abolished the production of anti‐gastric autoantibodies and decreased the incidence of gastric mononuclear infiltrates from the 69% observed in normal rat immunoglobulin (Ig)‐injected mice to 16%. Further, in mice treated with only a single dose of anti‐IFN‐γ immediately after thymectomy at 3 days after birth, the incidence of autoimmune gastritis was 1/19 compared to 8/19 in normal rat Ig‐injected mice. Prevention of autoimmunity by neutralization of IFN‐γ several weeks prior to the detection of a pathological lesion strongly suggests that IFN‐γ plays an essential role in the initiation of the gastric autoimmune response.