Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity

Int Rev Immunol. 2005 Jan-Apr;24(1-2):111-22. doi: 10.1080/08830180590884611.

Abstract

Human autoimmune gastritis (AIG) is a chronic inflammatory disorder of the gastric corpus. We have defined the antigen repertoire and the functional properties of in vivo activated CD4+ T cells derived from the gastric mucosa of patients with AIG. A remarkable proportion of the CD4+ T cell clones proliferated in response to H+,K+-ATPase. Six epitopes identified in the alpha chain, and 5 in the beta chain, of gastric K+,K+-ATPase were recognized by autoreactive gastric T cell clones. The majority of the autoreactive T cell clones secreted IFN-gamma and showed a T helper 1 (Th1) profile. All clones produced TNF-alpha,provided help for B cell immunoglobulin production, expressed perforin-mediated cytotoxicity, and most induced Fas-Fas ligand-mediated apoptosis. Data suggest that activation of gastric H+,K+-ATPase-specific Th1 T cells is crucial in the pathogenesis of human gastric autoimmunity and atrophy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmune Diseases / immunology*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Gastritis / immunology*
  • H(+)-K(+)-Exchanging ATPase / genetics
  • H(+)-K(+)-Exchanging ATPase / immunology*
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Helicobacter pylori / pathogenicity
  • Humans
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Sequence Alignment
  • Th1 Cells / enzymology
  • Th1 Cells / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • H(+)-K(+)-Exchanging ATPase