Enhancement of lymphokine-activated T killer cell tumor necrosis factor receptor mRNA transcription, tumor necrosis factor receptor membrane expression, and tumor necrosis factor/lymphotoxin release by IL-1 beta, IL-4, and IL-6 in vitro.
Co-culture with IL-2 can induce human T lymphocytes to proliferate and become nongenetically restricted, lymphokine-activated killer (LAK) cells in vitro. Our studies were conducted with long term cultured, human T-LAK cells from peripheral blood, which are 95 to 99% CD3+. We found that proliferating 7 to 10-day human T-LAK cells express TNFR, by using a 125I-TNF binding assay. Additional treatment of these cells with the cytokines IL-1 beta, IL-4, or IL-6 rapidly up-regulated 55-kDa TNFR mRNA transcription and doubled TNFR membrane expression. Further studies revealed that these cytokines also increased the release of TNF and lymphotoxin (LT). Antibody neutralization studies indicated that IL-1 induces release of both TNF and LT; however, IL-4 and IL-6 induce primarily LT release. These results further support the concept that these cytokines are involved in the regulation of TNF/LT release, TNFR synthesis, and TNFR membrane expression. It is apparent that cytokines and their membrane receptors are involved in the autocrine/paracrine control of T cell proliferation, differentiation, and expression of functional activity after IL-2 stimulation in vitro.
Dett
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Department of Molecular Biology & Biochemistry, University of California Irvine 92717.
Gatanaga
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Ininns
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Cappuccini
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Yamamoto
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Granger
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Gatanaga
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D001483:Base Sequence; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4