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Cytotoxic Activity of Lymphocytes¹

II. Studies on Mechanism of Lymphotoxin-Mediated Cytotoxicity

From the Departments of Medical Microbiology and Surgery, Stanford University School of Medicine, Stanford, California 94305

Abstract

Characteristics of the cytotoxicity caused by supernatants of lymphocytes activated in culture are presented. The cytotoxic factor (lymphotoxin, LT) from human spleen cells incubated with phytohemagglutinin in serum-free medium was partially purified by gel electrophoresis. The cells left on the monolayer after incubation with LT demonstrated no detectable abnormalities. Increased permeability of the cell membrane to ⁸⁶Rb did not occur. Incorporation of ³H-leucine or ³H-thymidine was unimpaired when related to the number of viable residual cells. Cells died and fell off the monolayer even as ³H-thymidine incorporation per cell was unchanged. Kinetic analysis indicates that cell death increases exponentially with time and is second order for the concentration of LT. Cell death is caused by a mechanism other than a general inhibition of protein or DNA synthesis.

Footnotes

¹ This work was supported in part by National Institutes of Health grant, NIH AM 12458-05.