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natural killer cells month download article/chapter ch11-induced apoptosis nk cells activated fas-mediated apoptosis nk cell membrane nk cells cultivated necrotic nk cells related subjects anti-apoptotic gene flip article cancer immunology privacy choices/manage cookies full article pdf fas/fas-ligand fas/fasl interactions nk cells release soluble fasl fas-fc protein check access instant access european economic area il-1β limits norway e-mail 10 december 1998 / accepted conditions privacy policy time-dependent decrease ann-charlotte johnsen cancer research time-dependent manner accepting optional cookies intact apoptotic machinery article haux journal finder publish key role article log immunotherapy article fas protein cells membrane fasl article cite information steady-state privacy policy personal data books a johan haux cancer immunotherapy optional cookies manage preferences il-2 stimulation

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         headline:The role of interleukin-2 in regulating the sensitivity of natural killer cells for Fas-mediated apoptosis
         description: The Fas/Fas-ligand (FasL) system seems to play a key role in regulating immunoresponses. Highly purified CD56+CD3− natural killer (NK) cells were found to be resistant to the apoptosis-inducing Fas mAb CH11 in the absence or in the presence of interleukin-2 (IL-2) for up to 3 days. However, NK cells activated with IL-2 for 3 days became apoptotic following combined treatment with CH11 and actinomycin D, suggesting the presence of an intact apoptotic machinery. In contrast, NK cells cultivated in IL-2 for 6 days became sensitive to CH11-induced apoptosis without addition of actinomycin D. At this time, a pronounced up-regulation of the Fas protein on the NK cell membrane was detected. By using reverse transcription/polymerase chain reaction it was found that the anti-apoptotic gene FLIP was strongly expressed in NK cells for up to 6 days of IL-2 stimulation. After day 6, a time-dependent decrease in the expression of FLIP was observed concomitantly with increased sensitivity for Fas-mediated apoptosis. The amount of apoptotic and necrotic NK cells in the presence of IL-2 increased in a time-dependent manner, reaching 40% at day 6 of culture. The amount of apoptotic and necrotic NK cells was reduced in the presence of Fas-Fc protein. In addition, IL-2 stimulated the NK cells to release soluble FasL in a time-dependent manner, whereas membrane FasL did not seem to increase in a similar manner. These results indicate that Fas/FasL interactions are involved in the down-regulation of IL-2-activated human NK cells.
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            Key words NK cells
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            Oncology
            Immunology
            Cancer Research
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      headline:The role of interleukin-2 in regulating the sensitivity of natural killer cells for Fas-mediated apoptosis
      description: The Fas/Fas-ligand (FasL) system seems to play a key role in regulating immunoresponses. Highly purified CD56+CD3− natural killer (NK) cells were found to be resistant to the apoptosis-inducing Fas mAb CH11 in the absence or in the presence of interleukin-2 (IL-2) for up to 3 days. However, NK cells activated with IL-2 for 3 days became apoptotic following combined treatment with CH11 and actinomycin D, suggesting the presence of an intact apoptotic machinery. In contrast, NK cells cultivated in IL-2 for 6 days became sensitive to CH11-induced apoptosis without addition of actinomycin D. At this time, a pronounced up-regulation of the Fas protein on the NK cell membrane was detected. By using reverse transcription/polymerase chain reaction it was found that the anti-apoptotic gene FLIP was strongly expressed in NK cells for up to 6 days of IL-2 stimulation. After day 6, a time-dependent decrease in the expression of FLIP was observed concomitantly with increased sensitivity for Fas-mediated apoptosis. The amount of apoptotic and necrotic NK cells in the presence of IL-2 increased in a time-dependent manner, reaching 40% at day 6 of culture. The amount of apoptotic and necrotic NK cells was reduced in the presence of Fas-Fc protein. In addition, IL-2 stimulated the NK cells to release soluble FasL in a time-dependent manner, whereas membrane FasL did not seem to increase in a similar manner. These results indicate that Fas/FasL interactions are involved in the down-regulation of IL-2-activated human NK cells.
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         Key words NK cells
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         Oncology
         Immunology
         Cancer Research
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