Human intestinal mucosal mononuclear cells exhibit lymphokine-activated killer cell activity

Previous investigations have shown that mononuclear cells present in human intestinal mucosa possess cytotoxic properties that are unique and different from those of cells circulating in the peripheral blood. We have further explored the cytolytic capacity of human intestinal mucosal mononuclear cells using both phenotypic and functional criteria. Using an immunoperoxidase technique on gut frozen sections, we failed to identify cells bearing surface markers displayed by natural killer cells and recognized by the monoclonal antibodies Leu7, Leu11, and Leu15. Freshly isolated human lamina proprial mononuclear cells (LPMC) were unable to lyse K562 target cells, even after using a variety of experimental conditions which included depletion of adherent cells, fractionation by Percoll gradients or panning with monoclonal antibodies, and treatment with a prostaglandin synthetase inhibitor or interferon-gamma. In contrast, when LPMC were cultured in the presence of the lymphokine interleukin 2 (IL 2), they displayed high levels of cytotoxicity against both K562 and Daudi target cells. Such cytolytic activity appeared after 1 or 2 days of culture, was dependent on the amount of IL 2 added to the cultures, was independent of plastic adherent cells, and could be inhibited by agents that block proliferation. Interferon-gamma, when used under experimental conditions identical to those adopted for IL 2, was unable to induce any significant cytotoxicity by LPMC or enhance the level of killing obtained by stimulation with IL 2 alone. This IL 2-induced, nonspecific cytotoxicity of LPMC probably represents a form of lymphokine-activated killer cell function similar to that recently described for human peripheral blood lymphocytes. In view of the absence of morphologic and functional evidence for natural killer cells in human intestinal mucosa, the phenomenon of lymphokine-activated killer cell activity displayed by LPMC may represent an alternate cytotoxic function potentially relevant to intestinal mucosa immunity.