A study of natural killer cells

Herman, Marian Jean
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These studies involved the isolation of populations of peripheral blood leukocytes enriched for large granular lymphocytes (LGL), cells thought to be responsible for natural killer activity. It was found that the degree of cytotoxicity of LGLs could be modulated by various substances, namely, PLC/PRF/5 cell supernatants, interferon, certain monosaccharides and prostaglandin E2. This modulation appears to be due, at least in part, to the regulation of interleukin-1 (TL-) production by LGLs. LGLs are able to produce TL- in response, not only to LPS and Staphlococcus aureus hut also to a variety of NK sensitive target cells. The degree of sensitivity of these cells, to NK lysis, correlates with their ability to stimulate TL-1 production by LGLs„ The observed decrease in cytotoxic activity of LGLs from patients with advanced malignant disease can be ascribed to a defect in TL-1 production by these LGLs, an effect which can be partially corrected by in vitro interferon treatment. Treatment of target cells with IL-1 increased cytotoxicity of cancer patients LGLs to normal levels. This effect r v , appears to he a result, of increased hi ruling of LGLs to the target cells. It is postulated, therefore, that LGLs, coming into contact with K562 cells, produce II.-l which acts on the target cells enhancing their ability to bind further LGLs and thereby increasing the cytotoxicity of the latter.
A Thesis Submitted to the Faculty of Medicine University of the Witwatersrand, Johannesburg for the Degree of Doctor of Philosophy