Characterization of a monocyte differentiation factor distinct from gamma-interferon, tumor necrosis factor, or G,M-colony-stimulating factor that regulates the growth and functional capabilities of the U937 monocytic cell line.

We have analyzed the characteristics and cellular sources of the T cell-derived lymphokines that affect the proliferation and the oxidative metabolic capabilities of the U937 monocytic cell line. Although gamma-interferon (gIFN) and tumor necrosis factor-alpha (TNFa) can, in high doses, inhibit the proliferation of U937 cells, the predominant antiproliferative factor produced by activated CD4+ and CD8+ T cells has a MW = 45-55 Kd, is resistant to heat treatment, and is distinct and independent from gIFN, TNFa, and GM-CSF. The inhibitory effect of this lymphokine on U937 cell growth requires an 18-24-hr induction period; thereafter, this growth arrest persists for up to 5 d, even in the absence of the factor. The lymphokine responsible for inducing oxidative metabolic capabilities in U937 cells is also a non-gIFN, heat-resistant, 45-55-Kd factor secreted by CD4+ and CD8+ cells, and we postulate that this differentiation factor is identical to the factor responsible for inhibiting U937 growth. These data demonstrate the prominent role of T cell-derived factors distinct from gIFN, TNFa, or GM-CSF in regulating the growth and functional capabilities of monocyte-lineage cells. Furthermore, the data suggest it may be appropriate to distinguish monocyte activation, in which cells at a given maturational stage develop a heightened ability to perform a particular function, from changes in the functional repertoire of cells acquired as a consequence of lymphokine-induced differentiation.