Human lymphokine-activated killer cell activity. Role of IL-2, IL-4, and IL-7
H. Stotter and M. T. Lotze
Surgery Branch, National Cancer Institute, Bethesda, Md.
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.
