Three major molecules have been recognized as IgE-binding structures on hematopoietic cells: the heterotrimeric high-affinity receptor for IgE (Fc epsilon RI), the low-affinity receptor for IgE (Fc epsilon RII/CD23) and the Mac-2/IgE-binding protein (epsilon BP). The latter has been shown to be expressed on polymorphonuclear neutrophils (PMN), where it regulates IgE-dependent activation. Experiments were undertaken to determine whether the IgE-binding capacity of PMN is mediated exclusively by this molecule. No detectable binding of human myeloma IgE to unstimulated PMN from normal volunteers could be evidenced. In contrast, PMN stimulated with granulocyte macrophage colony stimulating factor (GM-CSF) (500 U/ml) for 24 h displayed positive IgE binding. This binding was significantly inhibited in the presence of mAb directed against Mac-2/epsilon BP and also in the presence of anti-CD23 mAb, but not of anti-Fc epsilon RI mAb or isotype-matched controls. By flow cytometry, CD23 expression was detected on GM-CSF-primed PMN by several anti-CD23 mAb, including EBVCS-5, BB10 or Mab135, which recognize different epitopes. CD23 was also evidenced by immunocytochemistry in GM-CSF-primed PMN. By in situ hybridization, GM-CSF-treated PMN exhibited a hybridization signal for CD23 mRNA and the presence of the CD23b isoform-specific mRNA was detected by RT-PCR. These findings indicate that PMN can synthesize CD23 molecules under GM-CSF induction. This strong CD23 expression might be of physiopathological relevance in IgE-dependent activation during allergic processes.
Suppressor cells were demonstrated in the spleens of C3H/He mice carrying 3-methylcholantrene-induced fibrosarcomas. These cells inhibited the in vitro reactivity of normal lymphocytes to T- and B-cell mitogens. They disappeared within a few days after the tumor was surgically removed. Pretreatment of spleen cells (ScC) from tumor-bearing (TB) mice with either iron and a nagnet, antiserum against Thy 1.2 antigen plus complement, or antiserum against immunoglobulin plus complement demonstrated that the suppressor cells were adherent, non-T-cells bearing immunoglobulin at their surfaces. The suppressive effect could still be demonstrated by addition of SpC from TB mice 24 or 48 hours after phytohemagglutinin stimulation of normal SpC, SpC from TB C3H/He mice inhibited mitogen-induced stimulation of both C3H/He and DBA/2 lymphocytes. In T-cell-deprived TB C3H/He mice, suppressor cells were also observed and had the same characteristics as those in non-T-cell-deprived mice. In nude mice, however, although suppressor cells were active, they were not adherent and did not bear immunoglobulin at their surfaces. The existence of these suppressor cells may be one reason why the immune system of TB animals is unable to reject the tumor.
Purified human native third component of complement, C3, was found to inhibit in vitro natural killer (NK) cell cytotoxicity in both mouse and human systems. The effect was dose and time dependent, a 50% inhibition being reached with 190 nM C3 (35 ,ug/ml) added during the NK assay or after a 30-min preincubation of the effector cells with this C3 concentration. C3 was shown to act at the effector-cell population level because pretreatment of the target cells did not modify the NK lysis. The inhibition was not due to general cytotoxicity nor to cell agglutination. Moreover, another in vitro cytotoxicity system (represented by alloreactive cytotoxic lymphocytes) was not affected by purified C3. Structural analysis ofthe active part ofthe C3 molecule shows that the C3-induced inhibition is supported by the C3a fragment. Release of carboxyl-terminal arginine residue by carboxypeptidase B, converting C3a into des-Arg7-C3a, did not alter the inhibitory effect displayed by this fragment. These results suggest that C3a may play an important role in the regulation of NK activity.Natural killer (NK) cells are defined as spontaneously cytotoxic lymphocytes with broad target specificity mainly directed against tumor cells and virus-infected cell lines (1, 2), but the mechanisms controlling their cytotoxicity level are still poorly understood. In this regard, it has been shown that NK cell cytotoxicity can be strongly increased by interferons (IFNs) released during a viral infection (IFN-a) (3) or during the activation of T cells (IFN-'y) (4) and also by interleukin-2 (5). On the other hand, macrophages from mice injected with polyanions have been reported to exert suppressive effects upon NK activity (6, 7). Noteworthy findings are that macrophages are well known to express receptors for the native third component ofcomplement, C3, on their cell membrane (8) and also to synthesize C3 molecules (9). Moreover, bacteria and polyanions are activators of the alternative pathway of the complement in which C3 is the pivotal protein and a precursor of several fragments (10). Some of the C3 fragments have properties enabling reaction with cell surfaces through either acceptor sites (as for C3b) (11) or receptor sites (as for C3a, C3b, iC3b, and C3d) (8-12), and various biological functions have been associated with these fragments. Thus, C3a is an anaphylatoxin (13), and C3b (or iC3b and C3d) can mediate attachment of target particles and soluble complexes to macrophages and to B cells that express specific membrane receptors for these fragments, promoting in this way their specialized cell functions (14).Such data prompted us to investigate the possible functional relationship between C3 and NK activity. In this report, we show that highly purified human C3 has an inhibitory effect on in vitro mouse and human NK activities. This inhibition is dose and time dependent, acts at the effector-cell population level, and is carried by a small fragment of C3, the C3a. MATERIALS AND METHODSEffector Cells. Mouse spleen cells were ha...
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