Different Mechanisms of Resistance to Lymphokine-activated Killer (LAK) Cells in Leukemic Cell Sublines Selected by Etoposide or by LAK Cells

Abstract

Two models of in vitro induction of human IM-9 lymphoblastoid cell line resistance to LAK cell-mediated killing were compared. IM-9 cell line variants were selected in vitro by prolonged exposure to LAK cells or to etoposide. Sensitivity to killing by LAK cells or by etoposide, conjugation with LAK cells and surface marker patterns were compared. Both LAK-cell-selected cell subline (IM-9/SL-15) and etoposide-selected cell subline (IM-9/ER) have acquired resistance to LAK cell-mediated death. IM-9/ER cells, but not IM-9/SL-15 cells, were 3.2-fold less sensitive to etoposide as compared to parental IM-9 cells. IM-9/SL-15 cells revealed decreased conjugation with LAK cells and augmented CDlla/CD18 surface molecule expression as compared to IM-9 line. In contrast, IM-9/ER cells displayed a level of conjugation with LAK cells equal to IM-9 cells, but loss of CD11a/C18 expression. Our results suggest different mechanisms of acquired resistance to LAK cells are operative in etoposide- or LAK-selected sublines, involving deterioration of LFA-1 molecule expression and altered conjugation properties, respectively.

Keywords:

• Cell line IM-9
• LAK cells
• Selection
• Apoptosis
• Conjugation
• LFA-1