Interferon-γ is required during the initiation of an organ-specific autoimmune disease

Simon P. Barrett, Paul A. Gleeson, Harini De Silva, Ban Hock Toh, Ian R. Van Driel

Research output: Contribution to journalArticleResearchpeer-review

67 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1652-1655
Number of pages4
JournalEuropean Journal of Immunology
Volume26
Issue number7
DOIs
Publication statusPublished - 1996

Keywords

  • Autoimmunity
  • Gastritis
  • Interferon-γ
  • Thymectomy

Cite this