Radioresistance of culture-induced augmented natural killer-like activity |
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Authors: | C Brovall S M Levitz J J Ellner B Schacter |
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Affiliation: | From the Departments of Pediatrics, Medicine, and Pathology, Case Western Reserve University, Cleveland, OH 44106, USA |
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Abstract: | Human NK activity is radiosensitive under the control of X-linked genes. We have evaluated the expression of these genes in other forms of cellular cytotoxicity. The NK radioresistant and radiosensitive phenotype is expressed in ADCC. Specific cellular cytotoxicity, generated in a MLC with a radiosensitive donor as responder, was radioresistant. NK-like activity recruited from nonadherent cells of radiosensitive subjects stimulated with allogenic cells, mitogens (PHA, Con A or PWM), or recall antigens (TT or PPD) was radioresistant. The acquisition of radioresistance was relatively rapid, beginning within 24 hr after exposure to PHA, prior to detectable proliferation. Radioresistance of MLR augmented NK-like activity was maximal 3 days after initiation of the culture. MLR augmented NK-like activity was spared by the immunosuppressive polypeptide antibiotic CsA at doses up to 1 micrometer/ml. CsA did, however, reduce acquisition of radioresistance by the NK-like activity at doses above 0.01 mu gm/ml, a concentration which does not inhibit uptake of 3H-thymidine but does reduce the level of specific CML. These data suggest that mitogens and antigens, including allogeneic cells, are recruiting radioresistant NK-like activity which can be distinguished from the radiosensitive spontaneous NK activity of the cell donor. Further, in the MLR, both radiosensitive and radioresistant NK-like activity may be recruited. |
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Keywords: | ACDD antibody-dependent cellular cytotoxicity CML cell-mediated lympholysis CsA Cyclosporin A Con A Concanavalin A E/T effector to target ratio FCS fetal calf serum HRPMI Hepes buffered RPMI 1640 IL-2 Interleukin 2 MLC mixed lymphocyte culture MLR mixed lymphocyte reaction αNK augmented natural killer NK natural killer NSE nonspecific esterase PBMNC peripheral blood mononuclear cells PHA phytohemagglutinin PPD purified protein derivative PWM pokeweed mitogen TT tetanus toxoid |
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