Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis

Gastroenterology. 1996 Jun;110(6):1791-802. doi: 10.1053/gast.1996.v110.pm8964405.

Abstract

Background & aims: Murine autoimmune gastritis, induced by day-3 thymectomy, is characterized by cellular infiltrates and circulating autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. The aim of this study was to analyze the cellular infiltrates and cytokines in autoimmune gastritis.

Methods: Stomachs and blood samples from day-3 thymectomized BALB/c mice were obtained from 2 to 12 weeks after thymectomy for analysis.

Results: At 4 weeks, the gastritic infiltrates were composed of macrophages and CD4+ T cells, accompanied by major histocompatibility complex class II expression on gastric epithelial cells. Mucosal B cells, scant at 4 weeks, were abundant at 8 weeks, coincident with the peaking of autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. CD8+ T cells increased marginally during the 12 weeks. Mononuclear cells from diseased stomachs transferred gastritis to nu/nu recipients. At 4 weeks, interleukins 2, 3, 5, 6, and 10; interferon gamma; tumor necrosis factor alpha; and granulocyte-macrophage colony-stimulating factor were detected in gastritic mucosa, but interleukin 4 was not.

Conclusions: The early lesion of autoimmune gastritis is composed of macrophages and CD4+ T cells with major histocompatibility complex class II expression in gastric epithelial cells. Autoantibody production is a late event. Our results are consistent with a lesion mediated by CD4+ T cells producing a mix of Th1- and Th2-type cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / analysis
  • Autoantibodies / immunology
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / pathology*
  • Cell Movement
  • Cytokines / biosynthesis*
  • Flow Cytometry
  • Gastric Mucosa / immunology
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastritis / immunology
  • Gastritis / metabolism*
  • Gastritis / pathology*
  • H(+)-K(+)-Exchanging ATPase / immunology
  • Histocompatibility Antigens Class II / analysis
  • Immunohistochemistry
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Monocytes / physiology*
  • Phenotype

Substances

  • Autoantibodies
  • Cytokines
  • Histocompatibility Antigens Class II
  • H(+)-K(+)-Exchanging ATPase