The autocrine role of tumor necrosis factor in the proliferation and functional differentiation of human lymphokine-activated T killer cells (T-LAK) in vitro.
The autocrine role of tumor necrosis factor alpha (TNF) in the proliferation and functional differentiation of human lymphokine-activated T-killer cells (T-LAK) in vitro was investigated. Human peripheral blood lymphocytes initially stimulated with IL-2 and phytohemagglutinin-P (PHA) for 48 h will proliferate for long periods in vitro in the presence of IL-2. These T-LAK cells have been shown to be 95% CD3 positive. Employing ELISA techniques, greater than 500 pg/ml of TNF was found to be released in the supernatants of these cells during the first 5 days of culture. However, the levels dropped to 100-200 pg/ml by days 7-10. T-LAK cells grown from days 7 to 10 in the presence of IL-2 and rabbit anti-TNF were significantly growth inhibited (up to 23%). The cytolytic activity of T-LAK cells grown from days 0 to 7 in the presence of anti-TNF was also decreased (up to 75%). Phenotypic analysis of these anti-TNF treated T-LAK cells revealed a decrease in CD8 expression (up to 12%) and increase in CD4 expression (up to 27%) when compared with control cells. The data suggest that TNF has a regulatory role in the growth and functional differentiation of these human T-LAK cells.
Innins
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Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Gatanaga
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Van Eden
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Knudsen
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KL
Granger
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Gatanaga
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D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D014409:Tumor Necrosis Factor-alpha