Impaired T-cell regulation of B-cell growth in Helicobacter pylori--related gastric low-grade MALT lymphoma.

Abstract

Neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma are responsive to T helper cells and sensitive to withdrawal of H. pylori-induced T-cell help. The clonal progeny of T cells from the gastric mucosa of 5 patients with MALT lymphoma was compared with that of T-cell clones obtained from 5 H. pylori-infected patients with chronic gastritis. T-cell clones were assessed for specificity to H. pylori, cytokine profile, help for B-cell proliferation, and perforin- or Fas-mediated cytotoxic regulation of B-cell growth. Twenty-eight of 165 CD4(+) gastric clones from MALT lymphoma and 33 of 178 CD4(+) clones from chronic gastritis recognized H. pylori antigens. Cytokine production was similar in the 2 series of clones. All MALT lymphoma-derived clones dose-dependently increased their B-cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1 because of concomitant cytolytic killing of B cells. T-cell clones from MALT lymphoma had both reduced perforin-mediated cytotoxicity and poor ability to induce Fas-mediated apoptosis. These defects were limited to gastric T cells. H. pylori-induced T cell-dependent B-cell activation and deficient cytotoxic control of B-cell growth may link H. pylori infection, local T-cell response, and genesis of low-grade gastric MALT lymphoma.