CD4 + Th1-cells Predominate in Low-grade B-Cell Lymphoma of Gastric Mucosa-associated Lymphoid Tissue (MALT type)

Abstract

Background: Little is known about the function of T cells in the inflammatory infiltrate in Helicobacter pylori -associated gastritis and B-cell lymphoma of mucosa-associated lymphoid tissue (MALT type). Previous studies have proposed a dominant Th1-type response in low-grade MALT lymphoma consistent with the Th1 response observed in H. pylori -associated gastritis. Methods: We performed a novel flow cytometric approach in which CD3 panning for enrichment and activation of small numbers of T cells and intracellular cytokine analysis were combined to selectively characterize the cytokine profile of T cells (IFN- n for Th1) derived from the gastric mucosa of 23 patients with low-grade MALT lymphoma stage IEI 1 (lymphoma infiltration of mucosa/submucosa sparing the muscularis). Endosonography was performed in each case to control the depth of lymphoma infiltration. For comparison, 19 patients with H. pylori -positive gastritis were also analysed. Results: There was a CD4/CD8 ratio of 4 in patients with MALT lymphoma and of 2 in chronic gastritis. The proportion of IFN- n producing cells within the CD4- positive T-cell population in MALT lymphoma was 22%; in chronic gastritis it was 13% while no such difference could be encountered in CD8-positive T cells. Conclusions: The data point towards a dominant intratumoral IFN- n dominated T-cell response associated with early low-grade MALT lymphoma. A polarized IFN- n dominated Th1-type response may either contribute to the inability of the immune system to eradicate H. pylori infection, thereby promoting the activation status of the lymphocytic infiltrate in low-grade MALT lymphoma, or may mirror a concomitant tumor-specific T-cell response accompanying early stages of tumor progression.