Cytokine-induced killer cells against autologous CLL: Direct cytotoxic effects and induction of immune accessory molecules by interferon-γ

Abstract

Cytokine-induced killer cells (CIK cells), coexpressing CD3 and CD56, can be expanded from peripheral blood mononuclear cells by the timed addition of interferon-γ (IFN-γ), IL-2 and OKT3. The effects of CIK cells on primary, autologous CLL cells are described. We used MACS to separate CD3 + cells for expansion of CIK cell effectors and CD19+ targets from peripheral blood of 16 CLL patients. Apoptosis was assessed by measuring annexin V staining in CLL cells. After incubation of autologous CIK with CLL, specific apoptosis in CLL cells was 15%. Coincubation with irradiated CIK cells for 48 hr before adding vital CIK cells resulted in an increased ICAM-1 expression on CLL cells and an increase in apoptosis of CLL targets (30%). These effects were mediated by IFN-γ secretion of CIK cells. In addition to their direct cytotoxic effect, CIK cells secrete IFN-γ that modulates the expression of adhesion molecules on CLL cells, and this enhances apoptosis induction by cytotoxic effector cells. © 2006 Wiley-Liss, Inc.