The differential inhibitory effect of lymphotoxin and immune interferon on normal and malignant lymphoid cells.

Supernatants containing lymphotoxin (LT) and immune interferon (IFN-gamma) or IFN-gamma alone were produced by antigen-stimulated murine T cell clones. These lymphokine preparations as well as cloned recombinant murine IFN-gamma (Genentech) were tested for antiproliferative activity on a variety of murine T, B, macrophage, and mastocytoma tumors and on T cell clones and LPS-stimulated B cells. The growth of every cell line tested was susceptible to the LT-containing supernatants. Cloned recombinant murine IFN-gamma inhibited the growth of A9 fibroblasts but not L929 cells. Neither the cloned murine IFN-gamma nor that produced by a T cell clone had any appreciable effect on the lymphoid cells except for one B cell lymphoma, A20. The sensitivity of nontransformed T and B cells to LT indicates that this lymphokine may play an immunoregulatory role. Indeed, the T cells that produce LT are sensitive to its cytotoxic activity and, therefore, regulate themselves. The differential inhibitory effects of LT and IFN-gamma on lymphoid target cells allow us to distinguish between preparations that contain IFN-gamma alone and those that contain LT and IFN-gamma. The susceptibility of lymphoid tumors to the antiproliferative activity of the LT-containing preparations indicates that LT either alone or together with IFN-gamma may be useful in tumor therapy.