Differential Tumor Necrosis Factor Production by Human Monocyte Subsets

The human monocyte (MØ) subset rosetting with anti RH‐coated human erythrocytes via high‐affinity, 72 kD receptors (FcRI+), contains the PGE2‐producing immunosuppressive subpopulation, while the non‐rosetting MØ subset (FcRI‐) is the major plasminogen activator‐producing and antigen‐presenting MØ. This study gives additional evidence for the functional disparity of the FcRI‐ and FcRI+ MØ subsets. We are demonstrating that the normal human MØ subset isolated by rosetting via the FcRI receptor (FcRI+) produces greater quantities of tumor necrosis factor (TNF) than the non‐rosetting (FcRI‐) MØ. TNF production by the FcRI+ MØ subset is greater than that of the FcRI‐ MØ subset whether secreted (P < .001) or cell‐associated (P < .001) TNF is assessed. The rosetting MØ subset that expresses high densities of FcRI (FcRI+) produced the majority of normal human peripheral blood MØ TNF whether the stimulation was an interferon gamma (IFNγ) prime followed by MDP or followed by interleukin‐2 (IL‐2). The Fc rosetting technique itself resulted in some TNF induction in the FcRI+ MØ subset accounting for some of the increased TNF production of this subset. However, increasing the stimulation level of the FcRI very‐low‐density (FcRI‐) MØ subset did not induce it to produce TNF levels equivalent to the moderately stimulated FcRI+ MØ subset. These data, therefore, imply that only stimulation through the type I Fcγ receptor can augment or induce TNF activity. The difference in the MØ subset's TNF response remained even after the FcRI‐ MØ subset received a 2.5‐fold increase in stimulation with the classical MØ induction regimen of IFNγ plus bacterial cell wall product. Although stimulation of the FcRI+ MØ subset via crosslinking of their FcRI receptors might represent a unique TNF stimulation pathway, this stimulation does not occur in the low‐density FcRI (FcRI‐) MØ subset, again indicating functional disparity between these subsets. Greater TNF production by the FcRI+ MØ subset was induced concomitant to elevation of its prostaglandin E2 production. Since both TNF and PGE2 are increased in some patient groups, a pathological shift in the FcRI+ versus FcRI‐ MØ ratio in these patients coupled to the functional differences in FcRI+ and FcRI+ MØ subsets could be one mechanism for the development of immunoincompetence.