Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity.
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.
D'Elios
Mario M
MM
Department of Internal Medicine, University of Florence, Florence, Italy. delios@unifi.it
Amedei
Amedeo
A
Azzurri
Annalisa
A
Benagiano
Marisa
M
Del Prete
Gianfranco
G
Bergman
Mathijs P
MP
Vandenbroucke-Grauls
Christina M
CM
Appelmelk
Ben J
BJ
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005756:Gastritis / Q000276:immunology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D017506:H(+)-K(+)-Exchanging ATPase