Enhancement of cell-mediated cytotoxicity by Clostridium difficile toxin A: An in vitro study

W. Malorni, S. Paradisi, M. L. Dupuis, C. Fiorentini and C. Ramoni. Enhancement of cell-mediated cytotoxicity by Clostridium difficile toxin A: an in vitro study. Toxicon 29, 417–428, 1991.—Cells from the immune system exhibiting cytotoxic activity are able to kill tumor or infected cells in a major histocompatibility complex-restricted (cytotoxic lymphocytes) or nonrestricted (natural killer cells) manner. In order to exert such a cytotoxicity they have to bind the target cell and release cytotoxic factors able to induce target cell death. Treatment of human peripheral blood mononuclear cells with toxin A from Clostridium difficile induced an enhancement of the cytotoxic efficiency of these effector cells. Morphological analysis of effector/target cell pairs seems to suggest that this could be related to an increased ability of cytotoxic effectors to establish close and intertwined contacts with target cells. These contacts involve adhesion molecules and lead to the formation of a “closed chamber” which probably improves the efficacy of lytic factors and results in an increased cytotoxicity.