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The mechanisms associated with the modulation of immune response in the chronic phase of human schistosomiasis mansoni infection are complex and involve many cell types. In the present paper the authors demonstrate that antigenic stimulation of peripheral blood mononuclear cells (PBMC) from chronic-intestinal schistosomiasis mansoni patients with polyacrylamide beads (PB) conjugated to Schistosoma mansoni soluble egg antigens (PB-SEA) or adult worm antigen preparation (PB-SWAP) were able to induce a statistically significant increase on the in vitro multinucleated giant cell (MGC) formation after the 15th day in culture. A correlation between an increase in the number of MGC and a decrease in in vitro granuloma formation index to PB-SEA and PB-SWAP was observed. Moreover, the authors demonstrated a down-regulation of lymphocyte proliferative responses to S. mansoni antigens, during the differentiation pathway of monocytes towards MGC formation, due to a decrease in the antigen-presenting capacity of these cells. These phenomena also correlate with a concomitant decrease in the expression of HLA-DR and CD54 adhesion molecules on the surface of MGC. The results suggest that differentiation of monocytes to MGC may be one of the immunoregulatory mechanisms involved in the down-regulation of the granuloma reaction against S. mansoni eggs.

We examined the effect of interleukin-10 (IL-10), gamma interferon (IFN-gamma), phorbol ester (PDB), opsonized zymosan (OZ) and aminophylline (a cAMP phosphodiesterase inhibitor) on the reducing power and oxidizing species generation by human neutrophils, using MTT dye reduction and luminol-dependent chemiluminescence assays, respectively. Gamma interferon (IFN-gamma), phorbol ester (PDB) and opsonized zymosan (OZ) were activators while interleukin-10 (IL-10) and aminophylline were inhibitors. A strong parallelism was observed between oxidizing species generation and cellular reducing power in both activation and inhibition experiments. Our results also demonstrate for the first time the effect of IL-10 on free radical generation by neutrophils. The consequence of these activating and inhibiting effects on the inflammatory process are discussed.

Although multinucleated giant cells have been described for many years in association with different chronic inflammatory responses, their participation in immunoregulatory mechanisms within the schistosome egg granulomas remains to be clarified. In this study we determined if soluble egg antigen (SEA) or adult worm antigen preparations (SWAP) from S. mansoni induce giant cell formation in vitro and their relationship with the intensity of granulomatous reactivity. Antigenic stimulation of peripheral blood mononuclear cells (PBMC) from patients (N = 9) with active schistosomiasis infection increased giant cell formation per field after the 12th day in culture when treated with S. mansoni SEA conjugated to polyacrylamide beads (PB-SEA) (17 +/- 1.2) and SWAP (PB-SWAP) (18.5 +/- 1.5). The increase in the number of giant cells was statistically significant when compared to the control polyacrylamide beads (PB) (9 +/- 1.1) and purified protein derivative conjugated to beads (PB-PPD) (11.6 +/- 1.7). We also observed a correlation between an increase in the number of giant cells and a decrease in in vitro granuloma index (GI) to PB-SEA (GI decreased from 4.3 +/- 0.2 on the 6th day to 3.2 +/- 0.2 on the 12th day) and PB-SWAP (GI decreased from 4.8 +/- 0.3 on the 6th day to 3.5 +/- 0.05 on the 12th day). These data suggest that giant cell formation may be one of the immunoregulatory mechanisms involved in the down-regulation of the granuloma reaction against S. mansoni eggs.

The modulation of E receptors on T cells by anti-CD4 and/or anti-CD8 is reported. The percentage of E rosette-forming cells (RFC) was decreased when sheep erythrocyte and mononuclear cells were incubated in the presence of monoclonal antibodies anti-CD4 and/or anti-CD8. This inhibition was not due to shedding of the E receptor and it was reversed by 8-Br.-3',5' cyclic guanosine monophosphate (cGMP). In contrast, anti-HLA antibodies induced an enhancement of sheep erythrocyte receptor expression evaluated by RFC.