Biology and biochemistry of T cell-derived lymphokines. I. The coordinate synthesis of interleukin 2 and colony-stimulating factors in a murine T cell lymphoma.

Two cloned murine T cell lymphomas of identical lineage exhibit coordinate control of the synthesis of two lymphokines. One line, LBRM-33 5A4, growing in culture can be activated by phytohemagglutinin (PHA) to secrete Interleukin 2 (IL 2), a T cell growth factor, and colony-stimulating factor (CSF), a granulocyte/macrophage growth factor. In the absence of PHA, 5A4 cells do not produce IL 2 or CSF. The second line, LBRM-33 1A5, is incapable of IL 2 and CSF production after treatment with PHA. Stimulation of 1A5 cells with Interleukin 1 (IL 1) converts these cells to a state in which subsequent treatment with PHA leads to the production of IL 2 and CSF. When the 5A4 cell line is recloned, variant subclones can be isolated that do not produce IL 2 or CSF upon stimulation with PHA. The frequency of occurrence of nonproducing variants from 5A4 cells is approximately 1 in 20. Such clones appear to retain a stable nonproducer phenotype. Treatment of a number of these variant subclones with IL 1 prior to exposure to PHA results in the secretion of both IL 2 and CSF from cells. Thus, cell lines derived from cloned LBRM-33 tumor cells either produce both IL 2 and CSF upon stimulation with PHA or they do not produce either lymphokine. These results indicate that the synthesis of IL 2 and CSF in T cells may share common regulatory mechanisms. Further, the LBRM cells appear to be capable of oscillation between two phenotypes representing different states of lymphokine-producing cells.