Mansoni Antigens Research Articles

Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes.

Infection with Schistosoma mansoni (S. mansoni) or exposure to eggs from this helminth inhibits the development of type 1 diabetes in NOD mice. In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age. T cells from diabetes-protected mice make IL-10 in recall responses to parasite antigens. These cells are furthermore impaired in their ability to transfer diabetes to NOD-SCID recipients. Bone marrow dendritic cells derived from NOD mice are found to make more IL-10 and less IL-12 following culture with S. mansoni soluble egg antigens in conjunction with lipopolysaccharides. NOD mice are deficient in NKT cells. Soluble worm and egg antigens increase the numbers of V alpha 14i NKT cells in NOD mice. These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice.

Screening for intestinal helminth infestation in a semi-urban cohort of HIV-infected people in Uganda: a combination of techniques may enhance diagnostic yield in the absence of multiple stool samples.

Intestinal helminth prevalence is best determined by using multiple stool samples from each subject, but this may be difficult in the clinic or hospital setting. We used a range of well-established parasitological techniques in a study of interactions between helminth infestation and HIV in a cohort of 412 HIV-infected people in Entebbe, Uganda. Analysis of a single stool sample underestimated helminth prevalence, especially of low-intensity infections, but a combination of Kato-Katz smear, formol-ether concentration (FEC), charcoal culture for Strongyloides and a serum enzyme-linked immunosorbent assay for Schistosoma mansoni antigen (CAA) increased diagnostic yield. Helminths were diagnosed in 23% patients by FEC alone, 35% by FEC and Kato-Katz, 39% by FEC, Kato-Katz and charcoal culture and 49% by a combination of all three tests plus CAA. Performing a range of techniques on a single sample may enhance the detection of parasites. Techniques vary in their sensitivity for different helminths so the appropriate choice of techniques depends on which parasite species are being sought.

Human immune response in schistosomiasis: the role of P24 in the modulation of cellular reactivity to Schistosoma mansoni antigens

Schistosome antigenic components are being tested as vaccine candidates with various degrees of success, but there are only few reports using multivalent antigens to stimulate an appropriate immune response that leads to resistance or granuloma modulation. We investigated the in vitro response of peripheral blood mononuclear cells (PBMC) from chronic intestinal schistosomiasis individuals to PIII, a multivalent antigen prepared from Schistosoma mansoni adult worm antigen, and response to P24, a single antigen obtained from PIII. Treatment of PBMC with either PIII or P24 caused significant decrease in cellular proliferation and granuloma formation induced by S. mansoni antigens, and a significant elevation in IL-10 and TNF-α but not in IFN-γ production. Moreover, P24 promoted an elevation in TNF-α level on the in vitro granuloma reaction, when cocultured with polyacrylamide beads (PB) coupled to S. mansoni antigens. These findings suggest that, besides inducing protective immunity, PIII and P24 antigens seem to be important in the regulation of in vitro granuloma formation through stimulation of IL-10 and TNF-α production in human schistosomiasis. The more pronounced effect of P24 on reducing the in vitro granulomatous reaction could be associated with a balance between IL-10 and TNF-α production.

Infection with Schistosoma mansoni correlates with altered immune responses to Ascaris lumbricoides and hookworm

Studies were performed on humoral and cellular immune responses of patients from areas in Brazil endemic for hookworm and Ascaris lumbricoides, and either endemic or non-endemic for Schistosoma mansoni. Humoral and cellular responses were evaluated by enzyme-linked immunosorbant assay (ELISA) and peripheral blood mononuclear cell (PBMC) proliferation assays against larval hookworm antigens, A. lumbricoides egg antigens, and soluble egg antigens (SEA) or soluble whole adult antigenic preparation (SWAP) from S. mansoni. Patients from S. mansoni-endemic areas, who currently had only hookworm or Ascaris infections, expressed lower humoral and cellular responses to hookworm or Ascaris antigens, respectively, than did their counterparts from areas not endemic for S. mansoni. Individuals from S. mansoni endemic area, although without detectable S. mansoni infection, do mount humoral and cellular responses to SEA and SWAP. This group of individuals has been probably in contact with S. mansoni antigens, since the groups harboring A. lumbricoides or hookworm infections from non- S. mansoni endemic areas do not have detectable anti- S. mansoni responses. PBMC proliferative responses discriminated well between patients with active hookworm infections versus ascariasis, if they were from areas not endemic for S. mansoni.

Species-restricted antibody response against a DNA-construct coding for aspartic proteinase from Schistosoma japonicum.

DNA-based vaccine technology was used to immunize against the schistosome digestive enzyme, cathepsin D aspartic proteinase. The cDNA coding for Schistosomajaponicum aspartic proteinase was cloned in a mammalian expression vector under control of the CMV promoter/enhancer and expressed for the first time in transfected mammalian cells as well as in mice immunized--by means of intra-ear pinna injection--with the aspartic proteinase-encoding DNA construct. Mice developed antibodies which recognized the native protein in homogenates of S. japonicum worms and reacted with the gut and, to a much lesser degree, with the parenchyma of the parasites in cryostat sections. It was noteworthy that the vaccinated mouse sera did not detectably cross-react with S. mansoni antigens either in homogenates or on cryostat sections. By contrast, infection sera of mice or humans strongly cross-reacted with both schistosome species. We conclude that DNA vaccination can induce species-restricted antibody responses against schistosome proteins. The implications of this previously unrecognized specificity are discussed.

Signal transduction events in human peripheral blood mononuclear cells stimulated by schistosoma mansoni antigens

Activation of protein tyrosine kinases (PTKs) is a common step of T cell stimulation. However, the relationship between PTKs and activation of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients has not been explored yet. In this study, we investigated the participation of Lck and ZAP-70 protein tyrosine kinases (PTKs), as well as PLC-γ1 and Shc proteins in PBMC activation by Shistosoma mansoni antigens. PBMC were stimulated with SEA (soluble egg antigen) or SWAP (soluble worm preparation), lysed, precipitated with specific antibodies and the level of tyrosine phosphorylation evaluated. Our results show that Lck and Shc were phosphorylated upon stimulation of the cells with SWAP, as well as with SEA. However, the phosphorylation level was more pronounced in SWAP than in SEA-stimulated cells. Phosphorylation of ZAP-70 was observed only in SWAP stimulated cells. Additionally, PLC-γ1 phosphorylation was not observed in PBMC stimulated with SEA. Together, these results indicate that SEA and SWAP induce PBMC proliferation through distinct intracellular signaling pathways. Moreover, the weaker response of PBMC to SEA compared to SWAP stimulation suggests down-regulation of cells from intestinal chronic schistosomiasis patients to SEA, which may occur during immunomodulation to S. mansoni response.

HLA class II polymorphism influences onset and severity of pathology in Schistosoma mansoni-infected transgenic mice.

Genetic factors that might influence susceptibility or resistance in naive individuals and early-stage pathology in schistosomiasis are difficult to study in clinical trials, since in areas where the disease is endemic the first contact with the parasite occurs most often at very early ages. Therefore, four strains (DR1.Abeta degrees, DR2.Abeta degrees, DQ8.Abeta degrees, and DQ6.Abeta degrees ) of major histocompatibility complex class II-deficient mice (Abeta degrees ), transgenic for different HLA alleles, have been used to evaluate the potential role of HLA class II polymorphism in the onset of the infection by Schistosoma mansoni. The survival rates and parasitological and immunological parameters after infection were evaluated and compared against the control values obtained with Abeta degrees mice. All four mouse strains used in this study were able to generate a specific immune response against S. mansoni antigens (cytokine production and antibody production). However, only mice expressing DR alleles survived until the chronic stage of the infection and were able to mount protective granulomatous response avoiding hepatic damage, presenting predominant gamma interferon production. In contrast, strains expressing DQ alleles revealed an impairment in generating effective granulomas, resulting in earlier death, which was associated with an impaired hepatic granulomatous response and liquefactic necrosis, reflecting the influence of HLA polymorphism in the establishment of protective response in the early stage of infection.

The role of IL-10 and IgG1 in the protection and granulomatous response in Schistosomamansoni P24-immunized mice

Previous work by our laboratory identified a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, designated PIII, able to elicit significant in vitro cell proliferation, and lower in vitro and in vivo granuloma formation. In the present work, we investigated some biological activities of P24, an antigenic component of PIII. Immunization of mice with this antigen induced a significant protection degree against challenge infection and significant decrease in the hepatic granuloma formation. Pre-incubation of spleen cells from P24-immunized mice with S. mansoni antigens induced a significant increase of interleukin (IL)-10 levels, but not interferon-γ, in the cell supernatants. In addition, mice immunized with different S. mansoni antigens and P24 displayed indistinguishable levels of IgG2a in response to anti- S. mansoni antigens, while IgG1 levels were significantly increased. Collectively, our results indicate that P24 might mediate protective anti-parasite immunity and downregulate granulomatous hypersensitivity to S. mansoni eggs in part by its ability to induce a higher production of IgG1 and IL-10.

Human peripheral blood mononuclear cells stimulated by Schistosoma mansoni antigens: association between protein tyrosine kinases, mitogen-activated protein kinases and cytokine production

Concerning schistosomiasis, little is known about the intracellular signaling response of human peripheral blood mononuclear cells (PBMC) to Schistosoma mansoni antigens. To understand the critical role of protein tyrosine kinases (PTKs) in PBMC activation by S. mansoni antigens, we investigated how inhibition of PTKs by genistein, a tyrosine kinase inhibitor, affects proliferation, cytokine production and activation of mitogen-activated protein kinases (MAPKs). Our studies showed that PTKs have an important role in proliferation of PBMC from chronic schistosomiasis patients as cells stimulated with S. mansoni soluble antigens in the presence of genistein had an impaired proliferation. In contrast, PTK inhibition failed to cause any effect on MAPKs activity. We also evaluated the cytokine production for interleukin (IL)-2, interferon gamma (IFN-γ), and IL-10 in culture supernatants of PBMC treated with or without PTKs inhibitor. Our results show that PBMC from chronic patients produced a high amount of IL-10 when stimulated with soluble egg antigen preparation (SEA), however, the amount produced of IL-2 and IFN-γ was not significant. In the presence of PTKs inhibitor only the production of IL-10 was decreased. The findings suggest that PTKs are involved on signal transduction pathway for PBMC activation, but may not be an absolute requirement for all signaling responses to S. mansoni antigens.

Familial resemblance in humoral immune response to defined and crude Schistosoma mansoni antigens in an endemic area in Brazil.

This study addressed whether the humoral immune response to crude and defined Schistosoma mansoni antigens aggregates within families. The sample included 155 siblings from 42 nuclear families in Brazil. Sera examined by ELISA for antibody isotypes reactive to defined schistosome antigens and crude schistosome antigens (soluble adult worm antigen preparation and soluble egg antigen) demonstrated that there was a difference in sibling-pair correlations between defined and crude S. mansoni antigens. In contrast to the finding with crude antigens, egg-positive sibling pairs showed significant familial resemblance for all IgG subclasses and IgE to adult-stage antigens Smp20.8 and Smp50. Only the IgE and IgG4 isotypes showed familial resemblance to the egg-stage antigen, Smp40. Egg-negative sibling pairs showed significant familial resemblance only for IgE and IgG4 to Smp40. That both the IgE and IgG4 response to defined S. mansoni antigens showed familial resemblance is interesting in light of the converging evidence for the role of IgE and IgG4 in human susceptibility and resistance to reinfection.

Estimation of the local synthesis of immunoglobulin G (IgG) in the central nervous system of patients with spinal cord schistosomiasis by the IgG index

By analogy with other infections of the central nervous system (CNS), it is believed that schistosomal myeloradiculopathy (SMR) is an entity that may involve a mild-to-moderate degree of impairment of the blood-brain barrier along with intrathecal synthesis of antibodies. The first of these aspects is obvious but the second has not been clearly demonstrated. This study was undertaken in Brazil with the aim of investigating the production of immunoglobulin G (IgG) within the CNS in patients with SMR, by the determination of the cerebrospinal fluid (CSF) IgG index. The study population included 54 patients with SMR, evaluated prospectively. The CSF IgG index was increased in 43 of them (80%). Preliminary results from our laboratory suggest that these antibodies are reactive against Schistosoma mansoni antigens. Thus, this finding also suggests that this index may be useful in the differential diagnosis of SMR.

Recombinant vaccinia viruses and gene gun vectors expressing the large subunit of Schistosoma mansoni calpain used in a murine immunization-challenge model

Schistosomiasis is a parasitic disease affecting over 200 million people every year in tropical regions of the world. Drug treatment and other existing control measures are costly and have failed to eliminate the incidence of infection, morbidity and mortality due to Schistosoma mansoni infection. Vaccination of susceptible individuals using recombinant vaccines encoding key S. mansoni antigens may be the most effective and least expensive means of controlling schistosomiasis. A candidate vaccine antigen is p80, the large subunit of the S. mansoni protease, calpain. In our vaccine studies, we have employed both the wild-type p80 and a mutant p80 (mut p80) in which an active site amino acid was genetically altered to create a less proteolytically-active enzyme. Two vaccine delivery approaches were implemented using p80 or mut p80 as vaccine antigen: recombinant vaccinia virus (RVV) inoculation and DNA immunization via the Accell® gene gun (GG) delivery system. RVV's expressing p80 and mut p80 were generated and tested for recombinant protein expression in vitro. These RVV's were tested for protective capacity in mouse challenge studies. Neither subcutaneous nor intranasal vaccinations with RVV-p80 or RVV-mut p80 were capable of significantly reducing the mean worm burdens of vaccinated mice. A GG-RVV combination immunization regime using WRG-vectors encoding p80 and mut p80 for GG priming and the RVV's for boosting prior to S. mansoni challenge infection was performed and no significant protection was obtained over two repeated studies. However, duplicate challenge studies involving GG immunization of mice with WRG-vectors encoding p80 or mut p80 revealed that 3 inoculations of mice with WRG-full5′ mut p80 (containing the full 5′ untranslated region of mut p80) provided 60% protection which was statistically significant ( p<0.05). These preliminary in vivo studies demonstrate the potential for further study of the protection afforded by gene gun-delivered WRG-full5′ mut p80 into subsequently-challenged mice. Such studies may pave the way to effective vaccination of humans using WRG DNA vectors expressing a schistosomal calcium-activated neutral protease.

Production of monoclonal antibodies against target schistosomal antigen secreted in the urine of Schistosoma mansoni-infected patients

This study was undertaken to develop an immunodiagnostic test of active human schistosomiasis mansoni using a monoclonal antibody which targets urinary schistosomal antigen. Polyclonal antisera raised in rabbits against the processed urine of Schistosoma mansoni-infected patients showed very high and significant reactivity with ES product of ova compared with other different S. mansoni antigens. The monoclonal antibody (4.23) was reactive with repetitive epitopes of S. mansoni soluble egg antigen and ES product of ova with molecular mass range of 65–23 kDa and 80–23 kDa, respectively. It recognised different stages of the parasite life-cycle, with no cross reaction with Fasciola or hydatid antigen. MAbs were characterised by isotyping, immunoelectrophoresis, SDS–PAGE and the enzyme-linked immunoelectrotransfer blot technique, ELISA, and their recognition of carbohydrate or protein antigenic epitopes by periodate oxidation and trichloroacetic acid treatment of the antigen. It was used for detection of circulating schistosomal antigen in an antigen capture antibody sandwich ELISA on sera and urines of 58 S. mansoni-infected patients, 17 S. haematobium-infected patients, 15 parasite-free negative healthy controls and sera from 13 schistosomiasis-free patients harbouring Fasciola or hydatid infections. The percentage sensitivity of the assay in the serum of S. mansoni-infected patients was 98.4% and in urine 94.8%. A positive correlation was found between the number of faecal S. mansoni eggs and the circulating antigen, both in serum and in urine. Antigen circulating in urine correlated with that in the sera of S. mansoni patients. These data provide a sensitive and non-invasive method almost comparable with the use of sera for immunodiagnosis of schistosomiasis and an indirect way to reflect the intensity of infection. Australian Society for Parasitology.

Localization by Immunoelectron Microscopy of Schistosoma mansoni Antigens in the Glomerulus of the Hamster (Mesocricetus auratus) Kidney

Adult worm antigen (AWA) and soluble egg antigen (SEA) were localized ultrastructurally by immunoelectron microscopy using two monoclonal antibodies in the glomeruli of hamsters infected with Schistosoma mansoni cercariae or injected with S. mansoni eggs. AWA was detected in all cercaria-infected groups from the 30th day on and was present mainly in cytoplasm of mesangial cells, mesangial matrix, and glomerular basement membrane, either as isolated gold particles or in small electron-dense deposits of probable immune origin. AWA was encountered also on the inner side of the glomerular basal membrane, close to endothelial cells, and in the foot processes of the glomerular epithelial cells. SEA was detected at similar sites, apparently in lesser amounts, in uninfected hamsters inoculated with S. mansoni eggs into the jugular vein. Schistosomal antigens are apparently processed mainly by mesangial cells which are considered to be critical in the pathogenesis of S. mansoni associated glomerulopathy. Mesangioproliferative glomerulonephritis, immunoglobulin (IgG and IgM), and C₃ deposits were observed in hamsters in which AWA and SEA were visualized. During early phases of the infection and in hamsters in which granulomatous pneumonitis was induced by S. mansoni eggs, glomeruli were unchanged or showed a slight mesangial proliferation. Our findings suggests that egg antigens also contribute to the pathogenesis of experimental glomerulopathy in the hamster.

Cytokine Profile Associated to Effector Functions of Human T Cell Clones Specific for Schistosoma mansoni Antigens

T cell lines and clones specific for Schistosoma mansoni antigens were established to study cellular immunity in human schistosomiasis. Flow cytometric analysis of the clones demonstrated that all of them were of the helper inducer T cell subset (CD3 +, CD4 +, CD8 −), and expressed the αβ T cell receptor, besides the IL-2 low affinity receptor CD25. Lymphokine analysis revealed that clones presented Th 1, Th 2, or either Th 0 patterns of secretion. More interestingly, the capability of clones to induce in vitro granuloma reactions seems to be related to the presence of TNF-α and the absence of IL-10. In counterpart, IL-10 producer clones did not help in vitro granuloma formation, even in the presence of TNF-α.

Induction of protective immunity against Schistosoma mansoni infection by antigens purified from PIII, a fraction of adult worm, associated to the downregulation of granuloma formation.

This study was performed in order to define Schistosoma mansoni antigens able to function as modulator agents in BALB/c mice granulomatous hypersensitivity to parasite egg. The antigens P-24, P-35 and P-97 were purified by affinity chromatography from a fraction of S. mansoni adult worm antigenic preparation, denominated PIII, involved in the inhibition of granulomatous response to eggs. Immunization of mice with these antigens, in the presence of Corynebacterium parvum and Al(OH)3 as adjuvant, induced a significant protection degree against challenge infection, as observed by the decrease on worm burden recovered from portal system. In vitro blastogenesis assays revealed that purified antigens were able to induce significant proliferation of spleen cells from S. mansoni-infected mice. This protection was correlated to significant decrease in granuloma size induced by PIII. From these results, we concluded that PIII preparation contains antigens capable of mediating protective anti-parasite immunity and down-regulating granulomatous hypersensitivity to S. mansoni eggs.

Factors affecting high and low human IgE responses to schistosome worm antigens in an area of Brazil endemic for Schistosoma mansoni and hookworm.

We have previously examined the antibody isotype responses to schistosome worm and egg antigens in human populations living in areas of Kenya and the Philippines endemic for Schistosoma mansoni and S. japonicum, respectively. Here, we have analyzed antibody isotype responses to S. mansoni adult worm (AW) antigen and soluble egg antigen (SEA) in more than 500 Brazilian individuals, and found similar relationships with age and sex as in the Kenyan and Filipino populations. Isotype responses to AW antigen broadly increased with age whereas isotype responses to SEA decreased, and a higher proportion of males than females had detectable IgE against AW antigen. Most isotype responses to AW antigen and SEA correlated positively with intensity of infection with S. mansoni except AW antigen-specific IgG2, which correlated negatively. The overall prevalence of infection with S. mansoni in this area was relatively low at only 39.5%; hookworm prevalence was higher at 57.4%. The majority of those infected with S. mansoni were also infected with hookworm (76%). Those individuals with high IgE responses to AW antigen were matched for sex, age, and total IgG to AW antigen as closely as possible with individuals with low levels of AW antigen-specific IgE. The two groups were compared for factors potentially influential in IgE production. No difference was found between the high and low IgE responders for 1) intensity or prevalence of infection with S. mansoni, 2) relative exposure to S. mansoni, 3) number of previous treatments for schistosomiasis, or 4) prevalence of infection with hookworm, but differences were found in other isotype responses to S. mansoni. The high IgE responders had higher IgA and IgG4 against both AW antigen and SEA but lower IgG3 responses to AW antigen than the low IgE responders. The IgE responses to three S. mansoni antigens (paramyosin, Sm22.6, and a 12-kD AW antigen band) were detected in individuals with IgE against AW antigen only.

Antigenic recognition pattern of schistosomiasis patients bearing different parasite burdens.

Direct parasitological methods detect schisto-some eggs in stool or rectal mucosa. Immunologi-cal methods quantify the immune response to cer-tain Schistosoma mansoni antigens or the concen-tration of parasite-derived antigens in serum.Whereas the specificity of parasitological meth-ods usually comes close to 100%, the specificityof the immunological methods varies considerably.In the chronic phase of disease, when there arefew eggs in the feces, the infection is usually de-tected by immunological methods. However cross-reaction with other parasitic disease have beenobserved (NR Bergquist 1990 Mem Inst OswaldoCruz 87: 29-38, SML Montenegro 1992 Mem InstOswaldo Cruz 87: 333-335, H Feldemeir & GPoggensee 1993 Acta Tropica 52: 205-220). Thus,the use of chemically defined antigens and themolecular and immunological characterization ofthe parasite antigenic components are of utmostimportance.In the present communication we analyzed theantigenic recognition pattern of subjects bearingdifferent parasite burdens, aiming to identify diag-nostic antigens or markers of resistance.S. mansoni adult worms (Belo Horizonte-BHand Sao Lourenco da Mata-SLM strains) were col-lected by perfusion of mice seven weeks after in-fection with 200 cercaria. The worms were sepa-rated according to sex and stored in liquid nitro-gen. The life cycle stages of the parasites (egg,miracidium, cercariae, and schistosomulum) wereobtained and stored as above. Male and femaleadult worm soluble antigen was obtained and theprotein concentration determined by the methodof OH Lowry et al. (1951 J Biol Chem 193: 263-275).Patients infected with S. mansoni were fromSao Joaquim and Itapinassu-Tracunhaem, State ofPernambuco, Brazil. The patients were identifiedby two stool examinations (N Katz et al. 1972 RevInst Med Trop Sao Paulo 14: 397-400 ) and sepa-rated according to intensity of infections estab-lished by WHO (1993 Tech Report Series p. 830).Eight patients were selected: 4 with heavy infec-tion (HI) and 4 with light infection (LI). Blood wasobtained by venipuncture and serum was obtainedand stored at -20

The role of protein kinases in antigen-activation of peripheral blood mononuclear cells of Schistosoma mansoni infected individuals.

T cell recognition of antigens displayed on the surface of antigen presenting cell results in rapid activation of protein tyrosine kinases and kinase C. This process leads to second messengers, such as inositol phosphates and diacylgycerol, and phosphorylation of multiple proteins. The role of different protein kinases in the activation of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected individuals was evaluated using genistein and H-7, specific inhibitors of protein tyrosine kinase and kinase C, respectively. Our results showed that proliferation in response to soluble egg antigen or adult worm antigen preparation of S. mansoni was reduced when PBMC were cultured in presence of protein kinase inhibitors. Using these inhibitors on in vitro granuloma reaction, we also observed a marked reduction of granuloma index. Taken together, our results suggest that S. mansoni antigen activation of PBMC involves protein kinases activity.

IL-10 plays a role in the modulation of human granulomatous hypersensitivity against Schistosoma mansoni eggs induced by immune complexes.

It has been demonstrated that the chronic intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms that lead to a diminished granulomatous reaction to parasite eggs. Using an in vitro model of granuloma reaction we showed that immune complexes (IC) isolated from the sera of chronic intestinal schistosomiasis patients were able to reduce the granulomatous hypersensitivity (developed by peripheral blood mononuclear cells (PBMC) from schistosomiasis patients) to soluble egg antigen (SEA)-conjugated polyacrylamide beads (PB-SEA). This inhibitory activity, mediated by IC, was also observed in the proliferative response of PBMC stimulated with SEA and soluble worm antigen preparation (SWAP). Furthermore, we observed a decrease in TNF-alpha and an increase in IL-10 production by PBMC treated with IC in an in vitro granuloma reaction. This phenomenon was also seen in a cell proliferation assay when PBMC were treated with IC and stimulated with S. mansoni antigens. These results demonstrate that circulating IC may down-regulate PBMC reactivity to S. mansoni antigens by changing the cytokine pattern produced by these cells.