Expression of a gastric autoantigen in pancreatic islets results in non‐destructive insulitis after neonatal thymectomy

Simon P. Barrett, Ian R. Van Driel, Seong‐Seng ‐S Tan, Frank Alderuccio, Ban‐Hock ‐H Toh, Paul A. Gleeson

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23 Citations (Scopus)

Abstract

Autoimmune gastritis, induced by day‐3 thymectomy of BALB/c mice, is a destructive CD4+ T cell‐mediated disease characterized by leukocyte infiltrates in the gastric mucosa, loss of parietal and chief cells and anti‐gastric H/K ATPase autoantibodies. Our previous studies have indicated that a T cell response to the H/K ATPase β subunit is required for the onset of autoimmune gastritis (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419). To determine whether a response to the β subunit autoantigen is alone sufficient to induce autoimmunity, or whether other tissue‐specific factors are required, we have generated transgenic mice expressing the gastric H/K ATPase β subunit in β islet cells of the pancreas (RIP‐H/Kβ). RIP‐H/Kβ mice developed autoimmune gastritis and insulitis after day‐3 thymectomy. Significantly, insulitis, observed as a peri‐islet infiltrate, was only detected in thymectomized mice with autoimmune gastritis. There was no apparent immune destruction of the pancreas as insulitis did not progress to invasion of the islets or diabetes. Double transgenic mice, expressing the gastric H/K ATPase β subunit in the thymus and in the pancreas, were protected from both gastritis and insulitis after day‐3 thymectomy. Therefore, insulitis in the RIP‐H/Kβ mice appears to be dependent on a T cell response to the H/K ATPase β subunit. This is the first example where an organ‐specific initiating autoantigen has been expressed in another peripheral tissue. Autoimmune destruction in the stomach, but not the pancreas, indicates that tissue‐specific factors play a fundamental role in the development of organ‐specific autoimmunity.

Original languageEnglish
Pages (from-to)2686-2694
Number of pages9
JournalEuropean Journal of Immunology
Volume25
Issue number9
DOIs
Publication statusPublished - Sep 1995

Keywords

  • Autoimmunity
  • Gastritis
  • H
  • Insulitis
  • K ATPase
  • Peripheral tolerance

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