DIFFERENTIAL TUMOR-NECROSIS-FACTOR PRODUCTION BY HUMAN MONOCYTE SUBSETS

The human monocyte (M∅) 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 M∅ subset (FcRI-) is the major plasminogen activator-producing and antigen-presenting M∅. This study gives additional evidence for the functional disparity of the FcRI- and FcRI+ M∅ subsets. We are demonstrating that the normal human M∅ subset isolated by rosetting via the FcRI receptor (FcRI+) produces greater quantities of tumor necrosis factor (TNF) than the non-rosetting (FcRI-) M∅. TNF production by the FcRI+ M∅ subset is greater than that of the FcRI- M∅ subset whether secreted (P < .001) or cell-associated (P < .001) TNF is assessed. The rosetting M∅ subset that expresses high densities of FcRI (FcRI+) produced the majority of normal human peripheral blood M∅ 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+ M∅ subset accounting for some of the increased TNF production of this subset. However, increasing the stimulation level of the FcRI very-low-density (FcRI-) M∅ subset did not induce it to produce TNF levels equivalent to the moderately stimulated FcRI+ M∅ subset. These data, therefore, imply that only stimulation through the type I Fcγ receptor can augment or induce TNF activity. The difference in the M∅ subset's TNF response remained even after the FcRI- M∅ subset received a 2.5-fold increase in stimulation with the classical M∅ induction regimen of IFNγ plus bacterial cell wall product. Although stimulation of the FcRI+ M∅ 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-) M∅ subset, again indicating functional disparity between these subsets. Greater TNF production by the FcRI+ M∅ 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- M∅ ratio in these patients coupled to the functional differences in FcRI+ and FcRI- M∅ subsets could be one mechanism for the development of immunoincompetence.