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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
CD4+ Th1-cells predominate in low-grade B-cell lymphoma of gastric mucosa-associated lymphoid tissue (MALT type)
S Riedel1, M Kraft, T Kucharzik
1Dept. of Medicine B, Institute for Immunology and Institute for Microbiology, University of Münster, Germany. sriedel@uni-muenster.de
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-gamma for Th1) derived from the gastric mucosa of 23 patients with low-grade MALT lymphoma stage IEI1 (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-gamma 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-gamma dominated T-cell response associated with early low-grade MALT lymphoma. A polarized IFN-gamma 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.
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