Human lymphokine-activated killer cell activity. Role of IL-2, IL-4, and IL-7.
The T-cell growth factors interleukin 2 (IL-2) and interleukin 7 (IL-7) induce lymphokine-activated killer (LAK) cell activity in short-term cultures of human peripheral blood mononuclear cells. Interleukin 4 (IL-4), another T-cell growth factor, induces LAK cell activity in IL-2-prestimulated lymphocytes only and inhibits LAK cell generation in normal peripheral blood mononuclear cells. Our studies of the processes involved using 21-mer phosphorothioate antisense oligonucleotides to the sequence adjacent to the start codon of IL-2 mRNA or IL-4 mRNA (effective concentration, 5 to 10 mumol/L) and cyclosporine (0.01 to 1.0 microgram/mL) or FK506 (0.01 to 1.0 ng/mL) demonstrate that IL-7-induced LAK cell activity is independent of IL-2 production and is regulated by endogenously generated IL-4. Like IL-2, IL-7 stimulated production of tumor necrosis factor alpha, but we failed to detect interferon gamma in IL-7-stimulated cultures. The implication of this regulatory feedback in IL-7-induced LAK cell generation for clinical applications is discussed.
Stötter
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Surgery Branch, National Cancer Institute, Bethesda, Md.
Lotze
M T
MT
D016572:Cyclosporine / Q000494:pharmacology; D005246:Feedback; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008213:Lymphocyte Activation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology
D007376:Interleukin-2; D015851:Interleukin-7; D016376:Oligonucleotides, Antisense; D015847:Interleukin-4; D016572:Cyclosporine; D016559:Tacrolimus