A Physicochemical and Immunologic Comparison of the Cell Growth Inhibitory Activity of Human Lymphotoxins and Interferons in vitro

Abstract

The physicochemical, immunologic, and biologic relationships between human lymphotoxins (LT) and interferons (IF) present in supernatant fluids from lectin-stimulated peripheral blood lymphocytes (PBL) and a continuous B-lymphoblastoid cell line (PGLC-33h) were analyzed. LT activity obtained from lectin-activated PBL could not be resolved from IF activity by gel filtration chromatography. LT activity eluted in multiple peaks of activity at 70 to 90,000, and 40 to 50,000 m.w., characteristic of α and β LT, respectively. IF activity in these supernatant fluids eluted as a broad band between 35 and 80,000 m.w., also suggestive of molecular heterogeneity. In contrast, this m.w. heterogeneity was not observed in LT and IF activities obtained from the PGLC-33h cell line. LT and IF eluted as separate peaks of activity at 90,000 and 25,000 m.w., respectively. In addition, acid and heat lability of PGLC-33h IF suggested similarity to type II IF. Immunologic studies, with a rabbit anti-α class serum that neutralized LT activity from both PBL and PGLC-33h, did not affect IF activity from either of these sources. Supernatant fluids from PGLC-33h cultures were also capable of inhibiting the proliferation of HeLa cells in vitro. The growth inhibitory activity was attributed to LT- and IF-like molecules. This evidence suggests that although cytotoxic and anti-viral activities were due to separate molecules, LT and IF have overlapping biologic activities in their ability to inhibit the proliferation of cells in vitro.