Cytotoxic T cells in H. pylori-related gastric autoimmunity and gastric lymphoma.
Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop gastric B-cell lymphoma, gastric autoimmunity, or other life threatening diseases, as gastric cancer or peptic ulcer. The type of host immune response against H. pylori, particularly the cytolytic effector functions of T cells, is crucial for the outcome of the infection. T cells are potentially able to kill a target via different mechanisms, such as perforins or Fas-Fas ligand interaction. In H. pylori-infected patients with gastric autoimmunity cytolytic T cells, that cross-recognize different epitopes of H. pylori proteins and H(+)K(+)-ATPase autoantigen, infiltrate the gastric mucosa and lead to gastric atrophy via long-lasting activation of Fas ligand-mediated appotosis and perforin-induced cytotoxicity. On the other hand, gastric T cells from MALT lymphoma exhibit defective perforin- and Fas-Fas ligand-mediated killing of B cells, with consequent abnormal help for B-cell proliferation, suggesting that deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support both the onset and the promotion of low-grade B-cell lymphoma.
Bergman
Mathijs P
MP
Section Molecular Microbiology, Department of Molecular Cell Biology, VU University, 1081 HV, Amsterdam, The Netherlands.
D'Elios
Mario M
MM
D000818:Animals; D001327:Autoimmune Diseases; D004195:Disease Models, Animal; D016480:Helicobacter pylori; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone; D051379:Mice; D013274:Stomach Neoplasms; D013602:T-Lymphocytes, Cytotoxic