Chemical and Biological Properties of Human Lymphotoxin

Abstract

The cytotoxicity of lymphocytes toward allogeneic target cells in vitro was first shown by Govaerts (1960). This was later confirmed by Rosenau and Moon (1961). It was demonstrated that lymphocytes, when activated with antigen or mitogen, secrete a soluble cytotoxin which was named lymphotoxin (Granger and Kolb, 1968). Since then a number of established human lymphoid cell lines have also been reported to produce a similar cytotoxic molecule (Amino et al., 1974; Granger et al., 1970; Shacks et al., 1973; Papermaster et al., 1976). The activity of lymphotoxin has been tested against a number of cell lines both of animal and human origin. It has been demonstrated by several workers that lymphotoxin is both cytostatic and cytolytic to target cells (Evans and Heinbaugh, 1981; Rosenau, 1981; Sawada et al., 1976). Most of the biological studies with lymphotoxin have been performed with relatively crude preparations. The isolation of lymphotoxin has been a rather difficult task due to its heterogeneous nature and also because of the small amounts produced by normal lymphocytes and various lymphoid cell lines. We have purified human lymphotoxin from several hundred liters of cell conditioned medium derived from the lymphoblastoid cell line RPMI 1788. Using purified material we have also examined the in vitro effects of lymphotoxin on human tumor and normal cells.