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Cytostasis of Mouse and Human Monolayer Cell Cultures by Normal, Unstimulated Lymphocytes¹

From the Department of Surgery and the Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Abstract

The effect of increasing concentrations of mouse and human lymphocytes on the growth of tumor cells, in vitro, has been studied by three independent methods. Growth was measured by sequential counts of the cells sheeted in predetermined microscopic fields of the culture flasks, by electronic counts of harvested cells and by thymidine uptake studies. All assay methods used indicate that inhibition of target cell growth is proportional to the ratio of lymphocytes to target cells. Control studies demonstrated that the effect is not due to exhaustion of the medium, the release of toxic breakdown products or elaboration of humoral antibody by the lymphocytes. Cell contact between the two cell types is essential, but there is no evidence that a cytotoxic factor is released as a result of this contact. No evidence for the accidental inclusion of a mitogenic agent was found.

The inhibitory capability is reduced by prior irradiation of the lymphocytes and is lost following their disruption. It is possessed, to a significantly lesser degree, by thymocytes but not by peritoneal macrophages. This cytostatic ability appears to represent a genuine capacity of apparently normal lymphocytes.

Footnotes

¹ This investigation was supported by Grant PO2CA05837 from the National Cancer Institute and by the United Health Foundation.

² Wellcome Research Fellow. Present address: St. Mary's Hospital Medical School, London W2.