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Natural killer (NK) cells can be activated to produce IFN-gamma by lysate from Helicobacter pylori in combination with IL-12. Furthermore, NK cells in the gastrointestinal mucosa are likely to encounter H. pylori as well as other bacteria and may play a role in the mucosal innate immune defense. In this report, we show that in marked contrast to peripheral blood, the large majority of NK cells of human gastrointestinal mucosa lack CD8 expression. Importantly, we show that CD8(-) and CD8(+) NK cells have different functional properties; although the cytotoxic capacity of the different NK cell populations was equal, only CD8(-) NK cells were capable of responding by IFN-gamma production to stimulation with lysates from H. pylori and other bacteria - this was not due to an intrinsic defect in IFN-gamma production by CD8(+) NK cells. We propose that CD8(-) CD16(-) CD56(bright) NK cells constitute a subset of NK cells that is present in the gastrointestinal mucosa and is especially adapted to responding to bacterial infection by production of cytokines. These findings may have important implications for the understanding of NK cell subsets and the innate defense against gastrointestinal bacterial infections.

CD8<sup>–</sup> Natural Killer Cells Are Greatly Enriched in the Human Gastrointestinal Tract and Have the Capacity to Respond to Bacteria