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December 1991

Human Lymphokine-Activated Killer Cell ActivityRole of IL-2, IL-4, and IL-7

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).

Arch Surg. 1991;126(12):1525-1530. doi:10.1001/archsurg.1991.01410360099017

• 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)