Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis.

TLDR

Interferon, induced in lymphocytes by viruses or cell lines, markedly increases natural cytotoxicity of human lymphocytes against target cell lines. The study aims to determine whether interferon can stimulate efficient nonspecific cytotoxic cells while protecting normal cells, thereby enabling an inducible selective defense against tumor and virus‑infected cells. Interferon confers resistance to natural killer cell lysis on target cells via an intracellular mechanism that requires RNA and protein synthesis. Interferon boosts NK cell cytotoxicity by 70‑90% of total activity, yet simultaneously protects normal fibroblasts and reduces target cell susceptibility, while virus‑infected and most tumor cells remain vulnerable.

Abstract

Interferon, induced in lymphocytes either with viruses or cell lines, increases severalfold the natural cytotoxicity of human lymphocytes on target cell lines. Cell separation experiments support the hypothesis that interferon enhances the activity of natural killer cells rather than generating a new population of effector cells. In mixed culture of lymphocytes and cell lines in which endogenous interferon is produced, interferon mediates an enhancement of cytotoxicity that represents up to 70-90% of the observed cytotoxicity. The effect of interferon on target cells is antagonistic to the effect on the lymphocytes: the susceptibility to cell-mediated lysis of various cells upon pretreatment with interferon is decreased and in some cases almost completely suppressed. Interferon renders target cells resistant to natural killer cells acting by an intracellular mechanism which requires RNA and protein synthesis. While normal fibroblasts are protected, virus-infected cells and most tumor cells usually are not protected by interferon. Interferon by stimulating very efficient nonspecific cytotoxic cells and by protecting at the same time normal cells from lysis, might render the natural killer cell system an inducible selective defense mechanism against tumor and virus-infected cells.