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

Human autoimmune gastritis (ATG) 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.