Human Lymphokine-Activated Killer Cell Activity

Abstract

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.

Expression of IFN-γ Upon Triggering of Activating Ly49D NK Receptors In Vitro and In Vivo: Costimulation with IL-12 or IL-18 Overrides Inhibitory Receptors

“…This activation was selective, since IL-2, a known potent activator of NK cell lytic function, has little or no effect on IFN-␥ mRNA when combined with Ly49D activation. Likewise, IL-4 suppressed the activation via Ly49D, a result previously shown in human NK cells for generation of lymphokine-activated killer activity (24,25). The kinetics of mRNA and IFN-␥ production under these conditions are shown in Fig.…”

Multicomponent gene therapy vaccines for lung cancer: effective eradication of established murine tumors in vivo with interleukin-7/herpes simplex thymidine kinase-transduced autologous tumor and ex vivo activated dendritic cells

“…This suggests that the complete ance with these findings, IL-7 has been suggested both as an additional cytokine for the in vitro expansion of rejection of IL-7-modified tumor cells requires intact host immunity but non-T cell-mediated pathways for inhilymphocytes for adoptive transfer 23,24 and as a systemic agent for cancer immunotherapy. 38 We and others 27,45 bition of tumor growth are operative.…”

“…This could be due to IL-7, as well as through an IL-2-dependent pathway. 36 In addition, IL-7 enhances the generation of cytotoxic T one or more of several mechanisms: (1) a transduced tumor-mediated bystander effect; 25 (2) an IL-7-mediated cells 37 and LAK cells, 38 and induces cytokine secretion and tumoricidal activity in human peripheral blood monimmune response; 27,28 and/or (3) an IL-7-mediated antiproliferative response. 15 The bystander effect was also ocytes.…”

Interleukin-7 is a growth factor for Sézary lymphoma cells.

“…A fourth one was lost at week 6 by EBV B cell overgrowth. Reasons for failure to maintain other lines for longer period is unclear, however, IL7 have been reported to induce cytotoxic T cell generation (27)(28)(29). Cell lines were maintained in medium containing supernatant from a mouse stromal cell line containing the human IL7 gene by retroviral-mediated gene transfer (M2 lOB4-hIL7).…”