INTERACTION BETWEEN HUMAN INTERLEUKIN-2-ACTIVATED NATURAL-KILLER-CELLS AND HEAT-KILLED GERM TUBE FORMS OF CANDIDA-ALBICANS

Human interleukin-2-activated natural killer (LAK) cells are able to r ecognize and to bind to both Live and heat-killed germ tube forms of C andida albicans, establishing a wide and intimate contact as revealed by electron microscopic observations. Following the interaction, LAK c ells are activated: an increased expression of some cytokine mRNA (in particular, TNF-alpha, GM-CSF, and IFN-gamma) has been revealed by RT- PCR and perforin secretion has been suggested by immunofluorescence mi croscopy. Nonetheless, neither morphological damage or growth inhibiti on of fungal target cells have been detected. Instead, evident signs o f cell damage could be noticed in interacting LAK cells. Moreover, the observation by transmission electron microscopy of LAK cell-germ tube conjugates revealed the presence of apoptotic cells. The analysis of LAK cell cytotoxic activity against DAUDI cells showed that the lympho cytic effector underwent a significant reduction in its lytic capabili ty after the interaction with C. albicans. The results obtained in thi s in vitro study seem to indicate that in such an interaction LAK cell s cannot directly inhibit or kill the fungal pathogen by using their l ytic machinery but they secrete those cytokines which have stimulatory effects on phagocytic cells. The ultimate results are the programmed death of LAK cells and the enhancement of the fungicidal activity exer ted by competent cells. (C) 1998 Academic Press.