Immuno-suppressive effect of human macrophages. I. Evidence for an unstable soluble factor(s) inhibiting DNA synthesis and proliferation in PHA-stimulated lymphocytes.

Macrophages obtained by culturing blood monocytes in vitro for 8 days showed capacity to inhibit DNA synthesis and cell proliferation in PHA-stimulated lymphocytes separated from the macrophages by a membrane with pore size 0.2 micron. The DNA synthesis was measured as 3H thymidine incorporation and the proliferation as cell counts. The depression was reduced when the distance between macrophages and lymphocytes was increased concomitant with increased culture volume. Heat-killing of macrophages abolished their lymphocyte depressing capacity. Full inhibitory effect was established within 4 hours when lymphocytes were cultured in the proximity of macrophages. The effect was blocked by molecular filtration membranes with nominal molecular weight limits (nmwl) 1,000 and 10,000 whereas membranes with nmwl 25,000 only partially blocked the effect. No inhibitory effect was registered in the supernatants from macrophage-depressed lymphocyte cultures. Presumably the lymphocyte depressing effect is mediated via an unstable soluble factor(s).