Ability of cell-sized beads bearing tumor cell membrane proteins to stimulate LAK cells to secrete interferon-γ and tumor necrosis factor-α1

Anita S.F. Chong, J. Keith Pinkard, Kit S. Lam, Philip Scuderi, Evan M. Hersh, William J. Grimes

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We recently reported that lymphokine activated killer (LAK) cells were stimulated to release both interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) when stimulated by a variety of tumor cells. We proposed then that the released cytokines may play a role in mediating tumor cell regression in vivo. In this paper, we provide further information on the nature of the signals, provided by the tumor cells (K562 erythroleukemia), that stimulate LAK cells to secrete IFN-γ and TNF-α. Using a previously published protocol for coating tumor-membrane molecules onto cell-sized hydrophobic beads (also called pseudocytes), we demonstrate that the signal provided by the tumor cell is membrane associated. Beads coated with K562 membranes stimulated LAK cells to release IFN-γ and TNF-α. The pretreatment of these beads with trypsin and sodium periodate eliminated the ability of these pseudocytes to stimulate cytokine release in LAK cells. The glycoproteins that stimulate LAK cells to secrete IFN-γ and TNF-α were further enriched by their ability to bind concanavalin A (Con A, Jack Bean). To determine if the tumor-associated molecules that stimulate LAK cells to release IFN-γ and TNF-α are also the molecules involved in mediating tumor cell lysis, we tested the ability of the Con A binding and nonbinding proteins to inhibit the LAK cell-mediated lysis of K562 cells. Our results demonstrate that molecules that inhibited LAK cell-mediated cytotoxicity were not enriched by Con A. These results are therefore consistent with the conclusion that different sets of tumor-associated molecules are involved in the stimulation of LAK cells to secrete cytokine and in the induction of LAK cells to mediate tumor cell cytolysis.

Original languageEnglish (US)
Pages (from-to)96-110
Number of pages15
JournalCellular Immunology
Volume134
Issue number1
DOIs
StatePublished - Apr 15 1991

ASJC Scopus subject areas

  • Immunology

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