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Human Lymphokine-Activated Killer Cell ActivityRole of IL-2, IL-4, and IL-7
Hans Stötter, MD;
Michael T. Lotze, MD
Arch Surg. 1991;126(12):1525-1530.
Abstract
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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 µmol/L) and cyclosporine (0.01 to 1.0 µg/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.
(Arch Surg. 1991;126:1525-1530)
Author Affiliations
From the Surgery Branch, National Cancer Institute, Bethesda, Md (Drs Stotter and Lotze); and the Department of Surgery, University of Pittsburgh, Pa (Dr Lotze).
Footnotes
Accepted for publication September 1, 1991.
Presented at the 44th Annual Cancer Symposium of the Society of Surgical Oncology, Orlando, Fla, March 27, 1991.
Reprints not available. Correspondence to Section of Surgical Oncology, University of Pittsburgh, 497 Scaife Hall, Pittsburgh, PA 15261 (Dr Lotze).
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