concanavalin-a and Schistosomiasis

Eosinophil chemotactic activity in sera from mice undergoing an acute stage of schistosomiasis japonica and mansoni was examined. Eosinophilotactic activity in the serum was dependent on the dose and time of infection. Eosinophilotactic activity in sera from S. japonicum-infected mice was higher than that from S. mansoni-infected mice when they were compared at the comparable dose and time of infection. After gel chromatography on Sephadex G-200, eosinophilotactic activity in sera from mice infected with 30 cercariae of S. japonicum for 5 weeks was detected in the high molecular weight component. On the other hand, when sera from mice infected with 30 cercariae of S. japonicum for 8 weeks was chromatographed through Sephadex G-200 columns, eosinophilotactic activity was segregated into high (greater than 455,000) and low (less than 13,000) molecular weight components. High molecular weight ECF in sera from mice infected with 30 cercariae of S. japonicum for 8 weeks had high affinity to Con A, and was stable to heating or pronase digestion, but was sensitive to periodate oxidation, indicating its polysaccharide or glycoprotein nature. This high molecular weight ECF could be adsorbed by, and eluted from immunoaffinity beads coated with rabbit IgG anti-S. japonicum adult worm antibody. Thus, at least some part of circulating high molecular weight ECF would be derived from adult parasites.

Topics: Animals; Chemotactic Factors; Chemotactic Factors, Eosinophil; Chromatography, Affinity; Chromatography, Gel; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Male; Mice; Mice, Inbred BALB C; Molecular Weight; Schistosomiasis; Schistosomiasis japonica; Schistosomiasis mansoni

Natural killer (NK) cell activity against K-562 targets and lymphoproliferative responses to Con A, interleukin-2 (IL-2) and Con A + IL-2 were examined in a group of 41 Sudanese children suffering from schistosomiasis mansoni and haematobium. The results were correlated to the intensity of infection as determined by enumeration of parasite ova in urine and stool. NK cell activity measured at three effector to target cell ratios was significantly depressed in the patient group as compared to a German control group. Impairment of NK cell activity showed a direct relationship with the patients' parasite load. Furthermore lymphoproliferation to Con A, IL-2 and Con A + IL-2 was depressed in the group of patients. Interestingly the costimulation effect of IL-2 expressed as coefficient of delta ct/min(Con A + IL-2)/delta ct/minCon A correlated significantly to the intensity of infection suggesting that lymphocytes from heavily infected patients were defective in producing appropriate amounts of IL-2 in response to Con A. Our findings support the concept that heavy infections with S. mansoni and/or S. haematobium induce a peculiar dichotomy of cellular and humoral immune parameters. Whereas T cell-dependent cellular immune responsiveness and NK cell function decrease with increasing worm burden specific IgE and IgG antibody responses increase.

Topics: Cells, Cultured; Child; Concanavalin A; Feces; Humans; Interleukin-2; Killer Cells, Natural; Lymphocyte Activation; Lymphocytes; Mitosis; Parasite Egg Count; Schistosomiasis

Purified human eosinophils were treated with peripheral blood mononuclear cell supernatants containing eosinophil cytotoxic enhancing activity (ECEA). Schistosomula of Schistosoma mansoni which had been coated either with antibody (Ab) from the sera of infected patients or with the lectin concanavalin A (Con A) were incubated with ECEA-treated and untreated cells for 2 minutes to 12 hours and examined ultrastructurally. Killing was assayed at 18 hours. ECEA caused an increase in the killing of Ab-coated worms, but Con-A-coated worms were not killed by either ECEA-treated or untreated cells. Eosinophils began to degranulate on Ab-coated worms within 2 minutes and continued to degranulate, so that by 12 hours about half of the parasites had greater than 50% of their surface covered by discharge material. The ECEA-treated cells degranulated more than the untreated cells. There was much less discharge material on Con-A-coated worms than on Ab-coated worms. Eosinophils adhered to discharge material on the surface of both Ab- and Con-A-coated parasites. At 3 and 12 hours, lysed cells and cell fragments were also seen adhering to discharge material. In the absence of discharge material the cells adhered to residual glycocalyx or to the tegumental outer membrane. These studies suggest that eosinophils kill schistosomula by progressively degranulating onto their surface over many hours and that the increased toxicity caused by ECEA is due to an increase in discharge.

Topics: Antibodies; Cell Adhesion; Cell Separation; Cell Survival; Cells, Cultured; Concanavalin A; Eosinophils; Humans; Microscopy, Electron; Neutrophils; Schistosoma mansoni; Schistosomiasis

Peripheral blood mononuclear cells from 29 Sudanese children heavily infected with Schistosoma haematobium and S. mansoni were examined for lymphocyte subpopulations, for mitogen responsiveness in the absence and presence of interleukin-2 (IL-2), and for natural killer (NK) cell activity. The nutritional status was assessed by anthropometric and biochemical measurements. In comparison with a group of healthy Caucasian individuals the children with schistosomiasis showed a profound alteration of their cellular immune variables, reflecting a severe acquired immunodeficiency syndrome. The T-cell compartment, in particular the OKT4+ helper/inducer subset, was numerically reduced at the expense of an increased B-cell compartment. The patients' OKT4/OKT8 ratios were significantly diminished (median, 1.2; 95% confidence limits, 0.8-1.7) corresponding to a decreased responsiveness to the T-cell mitogen concanavalin A. Since addition of exogeneous IL-2 significantly enhanced the patients' lymphocyte proliferation in response to Con A, a defective IL-2 production was assumed to be at the origin of the impaired mitogenic response in chronic schistosomiasis. With regard to NK cell activity, most patients' lymphocytes failed to mediate significant cytotoxicity against the K562 target cell line, although normal percentages of cells with the NK phenotype (HNK-1+) were present. The results are discussed in view of immunological alterations seen in other parasitic infections with a heavy parasitic load.

Topics: Child; Concanavalin A; Cytotoxicity, Immunologic; Histocytochemistry; Humans; Interleukin-2; Killer Cells, Natural; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Phenotype; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

We have postulated that an insufficient active of collagenase relative to increased collagen synthesis may be the cause of the increased collagen accumulation in fibrotic tissues. In the present study, 125I-collagenase and rabbit anti-collagenase immunoglobulin G were used to develop a sensitive radioimmunoassay that detects 0.1 nM (3 ng) of collagenase protein in tissue samples. The assay also can detect collagenase protein that is associated with extracellular-matrix collagen fibrils. Good correlation with an assay of enzyme activity validates the radioimmunoassay for quantification of collagenase. The assay was used to measure amounts of collagenase in relation to fibrotic processes in livers of mice with schistosomiasis. Results indicate that the amounts of collagenase relative to synthesized collagens were significantly lower, and this may contribute to the progressive fibrosis. The occurrence of a maximum amount of collagenase at 7 weeks after infection with Schistosoma mansoni cercariae in concanavalin A-treated animals, as compared with 8 weeks in controls, could account for the large remission of fibrosis in mice so treated. The results emphasize the possible importance of collagenase in controlling or limiting fibrosis.

Topics: Collagen; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Immunoglobulin G; Liver; Microbial Collagenase; Radioimmunoassay; Schistosoma mansoni; Schistosomiasis

Spleen cells from mice harboring infections of Schistosoma mansoni for 20 weeks exposed to Con A or to soluble schistosome egg antigenic preparation (SEA), treated with Mitomycin C (Mc), and cocultured with spleen cells from either normal or infected mice caused an augmented baseline [3H]TdR incorporation by the otherwise unstimulated responder cells. This regulation required an in vitro induction phase. SEA-exposed, Mc-treated normal spleen cells had no effect on responder cell cultures. SEA-stimulated, Mc-treated chronic spleen cell augmentation was effective on responder cell populations from either normal mice or mice infected with S. mansoni for 8 weeks. Augmentation was most pronounced when assayed on cells from infected mice assayed over a 5-day incubation. In addition, it is demonstrated that these Con A- and SEA-elicited activities are mediated by soluble mediators which lack H-2 restriction.

Topics: Animals; Antigens; Concanavalin A; Disease Models, Animal; DNA Replication; Female; Kinetics; Lymphocyte Activation; Lymphocytes; Male; Mice; Mice, Inbred CBA; Ovum; Schistosoma mansoni; Schistosomiasis; Spleen

Previous studies have shown that eosinophils from eosinophilic individuals differ functionally from those of normal individuals. In order to test whether agents that might induce eosinophilia could also affect eosinophil function, we have compared the capacity of culture supernatants from mononuclear cells of eosinophilic or normal individuals to enhance eosinophil activity, as reflected by an increased killing of schistosomula of Schistosoma mansoni in vitro. An enhancing activity was detected, which increased both the antibody-dependent, and to some extent the antibody-independent killing of schistosomula by eosinophils, in the absence of complement. Under similar conditions, the supernatants failed to stimulate an otherwise undetectable neutrophil-mediated killing. The activity could be removed from the assay by washing, without reversing previous eosinophil stimulation, and was not directly toxic to the schistosomula. Preliminary characterization of the activity indicated that it was relatively heat-stable at 100 degrees C for 30 min, and had an estimated molecular weight of 35,000-45,000 as judged by G-200 Sephadex fractionation. The activity was produced by a nonlymphocytic, nonspecific esterase-containing adherent mononuclear cell in the absence of either Con A or antigenic stimulation. Significant enhancing activity was detectable after 1 h of culture and continued for at least 25 h. Protein synthesis was required for its production or release. Although the activity was detectable in supernatants from both eosinophilic and normal individuals, the supernatants that demonstrated highest activity and that could be titrated out furthest were generally derived from eosinophilic individuals, suggesting that there might be some association between eosinophilia and enhanced eosinophil function.

Topics: Animals; Cells, Cultured; Concanavalin A; Cytotoxicity, Immunologic; Emetine; Eosinophilia; Eosinophils; Humans; Lymphocytes; Monocytes; Schistosoma mansoni; Schistosomiasis

Crude polysaccharide antigen was extracted from Schistosoma mansoni egg homogenate by 44% aqueous phenol. The aqueous soluble polysaccharide extract was subjected to affinity chromatography with concanavalin A-Sepharose 4B. Two fractions (bound and unbound) were obtained; both of them gave precipitin lines with serum obtained from mice infected with S. mansoni. These precipitin lines gave partial identity. Further fractionation with wheat germ agglutinin-sepharose of the unbound fraction resulted in three antigenic fractions. These different antigens were eluted with different N-acetylglucosamine molarities (0, 0.05) and 0.5) and gave lines of identity when reacted against infected mouse serum. When the four antigenic materials were subjected to polyacrylamide gel electrophoresis and stained for proteins and polysaccharides no migration bands were observed. The chemical analysis of the two initial fractions showed a small percentage of amino acids in both fractions. Sugar analysis with gas-liquid chromatography showed different sugar composition of the two initial fractions.

Topics: Amino Acids; Animals; Antigens; Chromatography, Affinity; Concanavalin A; Female; Flame Ionization; Immunodiffusion; Lectins; Mice; Ovum; Polysaccharides; Schistosoma mansoni; Schistosomiasis; Wheat Germ Agglutinins

Purified human blood eosinophils, when incubated in human placental conditioned medium (a source of colony-stimulating factors) [CSF]) demonstrate an enhanced ability to damage antibody- or complement-coated schistosomula. This enhancement represents a 4- to 10-fold increase of eosinophil schistosomicidal ability and a 10-fold lowering of the threshold for antibody or complement required in the killing reaction. The activity that enhances eosinophil cytotoxicity and the eosinophil colony-stimulating activity in the placental conditioned medium are eluted in the same fraction (CSF-alpha) after chromatography on Sephadex G-100 and phenyl-Sepharose columns, suggesting that these two activities might be associated with the same molecule. CSF-alpha enhances the adherence step of the killing reaction: antibody-coated larvae were frequently found covered by several layers of eosinophils in tubes containing CSF-alpha. Such a degree of adherence was rarely seen in control tubes lacking CSF-alpha. This enhancement of the eosinophil adherence is detectable 45-60 min after addition of CSF-alpha to the culture. It is not affected by washing the cells after a short time of preincubation with CSF-alpha, and it occurs in the absence of protein synthesis, whereas colony-stimulating activity requires continuous protein synthesis and ceases when CSF is removed from the culture. Finally, CSF-alpha enhances the temperature-dependent reaction that insures the irreversibility of eosinophil attachment to schistosomula. These observations suggest that eosinopoietic factors could be responsible for some of the modified properties of blood eosinophils in eosinophilic individuals.

Topics: Antibody-Dependent Cell Cytotoxicity; Cell Adhesion; Colony-Stimulating Factors; Concanavalin A; Culture Media; Cytotoxicity, Immunologic; Eosinophils; Female; Humans; Pregnancy; Protein Biosynthesis; Puromycin; Schistosomiasis; Temperature

Parameters of in vitro cell-mediated immunity (CMI) have been measured in the local Kenyan population infected with Schistosoma mansoni. Lymphocyte responses to the non-specific T cell mitogens Concanavalin A (Con A) and Phytohaemagglutinin (PHA) were reduced in about 60% of schistosomiasis patients. Lymphocytes from control uninfected, and S. mansoni-infected donors formed equal numbers of spontaneous rosettes with sheep red blood cells, indicating that there was no over-all reduction in the percentage numbers of T cells in the schistosomiasis patients.

Topics: Adolescent; Adult; Child; Concanavalin A; Humans; Immunity, Cellular; Lymphocyte Activation; Middle Aged; Phytohemagglutinins; Rosette Formation; Schistosoma mansoni; Schistosomiasis; T-Lymphocytes

Topics: Animals; Antigen-Antibody Complex; Antigens; Concanavalin A; Female; Immunity, Cellular; Lymphocyte Activation; Lymphocytes; Male; Papio; Phytohemagglutinins; Schistosoma mansoni; Schistosomiasis; Time Factors; Trypsin

Plastic adherent peritoneal cells from Schistosoma mansoni-infected mice have previously been shown to exhibit nonspecific tumoricidal activity in vitro. In this report we show that these same cell populations kill significant numbers of skin-stage schistosomula in vitro in the absence of added antibody. Larval killing by these activated cells could be enhanced by the use of suspension rather than monolayer cultures and by addition of heat-inactivated immune mouse serum to the cultures. Adherence of cells to schistosomula was also enhanced under the same conditions, suggesting that cell binding to the larvae might be critical in the development or expression of microbicidal activity. In support of this hypothesis, the same level of enhancement of cell binding and larval damage was observed upon substitution of concanavalin A for immune mouse serum. Killing of schistosomula appeared to be mediated solely by activated macrophages in the peritoneal cell suspensions from S. mansoni-infected mice, because partially purified preparations of eosinophils were virtually inactive in these assays. Likewise, inflammatory macrophages from uninfected mice were unable to kill schistosomula under the same conditions, emphasizing the importance of activation in the development of killing capability. The finding that macrophages activated as a consequence of S. mansoni infection are able to kill larval schistosomes in vitro suggests that these cells may play a role in concomitant immunity to schistosomiasis in vivo.

Topics: Animals; Antibody-Dependent Cell Cytotoxicity; Ascitic Fluid; Concanavalin A; Eosinophils; Female; Immune Sera; Immunity, Cellular; Macrophage Activation; Macrophages; Mice; Mice, Inbred CBA; Rats; Rats, Inbred Strains; Schistosoma mansoni; Schistosomiasis

The nature of the mononuclear suppressor cell and the fraction of crude soluble egg antigen (SEA) capable of activating antigen-specific suppressor cells were studied in 32 Egyptian children infected with schistosomiasis mansoni. Crude SEA was fractionated on Con A Sepharose, and the unbound and bound material (eluted with alpha-methyl-D-mannoside) was recovered for use in the generation of suppressor cells by the use of a co-culture technique. The glycoprotein fraction was further purified by DEAE cellulose chromatography to isolate the major serologic antigen (MSA-1). We found that both the crude SEA and the "protein" fraction (nonadherent to Con A Sepharose) of SEA was capable of inducing antigen-specific suppressor cell activity in a dose-dependent manner. The glycoprotein fraction of SEA (including MSA-1) was responsible for inducing nonspecific suppression. The antigen-specific suppressor cell was characterized in terms of its adherence properties of plastic and the presence of a receptor for sheep erythrocytes (E). The nonadherent, E-rosette-positive mononuclear cells were found to be activated by the crude SEA, and the "protein" fraction of SEA was found to exert an antigen-specific suppressor influence. Clinically, suppressor cell activity was found to be statistically greater in patients with a high intensity of infection compared to those with a low intensity of infection, but it was not different in patients with regard to the presence or absence of organomegaly. These results provide further information on one of the immunoregulatory mechanisms operative in human S. mansoni infection and on the nature of the antigen(s) that activates this response during the course of infection.

Topics: Antigens; Cell Adhesion; Chemical Fractionation; Child; Concanavalin A; Epitopes; Female; Humans; Lymphocyte Activation; Lymphocytes; Ovum; Rosette Formation; Schistosomiasis; Sepharose; T-Lymphocytes, Regulatory

Topics: Animals; Antigen-Antibody Complex; Antigens, Surface; Carbohydrates; Concanavalin A; Immune Sera; Membrane Proteins; Mice; Molecular Weight; Schistosoma mansoni; Schistosomiasis; Trypsin

Schistosoma mansoni is known to release an inhibitory factor of lymphocyte proliferation elicited in vitro. The effect of this dialyzable schistosome incubation product (DSIP) was tested in vivo on different aspects of the cell-mediated immune response. First, the DSIP injected into C57B1/6 mice markedly inhibited the delayed type hypersensitivity to sheep red blood cells (SRBC). Furthermore, the DSIP injected into S. mansoni infected Fisher rats at the beginning of the infection induced an inhibition of the specific lymphocyte response to S. mansoni antigen and of the spleen cell response to concanavalin A (Con A). The DSIP injected into uninfected rats also inhibited the spleen cell response to Con A. In uninfected as in infected rats injected with the DSIP, the lymphocyte response to Con A was restored after purification of the spleen cells on a nylon wool column. Moreover spleen cells from rats injected wtih the DSIP reduced the proliferative response of normal syngeneic spleen cells induced by Con A. This inhibition was not observed when cells from DSIP-injected rats were previously passed through a nylon wool column. In contrast, nylon wool depletion of spleen cells from infected rats injected with the DSIP did not restore the lymphocyte response to S. mansoni antigen. It seems tht DSIP could partly explain the modulation of the cellular immune responses observed during S. mansoni infection and could represent one of the mechanisms of this parasite's survival in the immunized host.

Topics: Animals; Cell Division; Concanavalin A; Hypersensitivity, Delayed; Immunity, Cellular; In Vitro Techniques; Lymphocytes; Mice; Mice, Inbred C57BL; Rats; Schistosoma mansoni; Schistosomiasis; Sheep; Spleen

Serum taken from baboons infected with Schistosoma mansoni was able to suppress in vitro reactivity of normal baboon lymphocytes. The concanavalin A response was significantly suppressed by such serum, whereas the specific suppression of the phytohaemagglutinin response was minimal. Serum from S. mansoni infected donors also depressed the mixed lymphocyte reactions to xenogeneic targets, but did not affect the specific transformation of lymphocytes stimulated with a parasite Ag. Significant suppressive activity occurred in the baboon serum from 4 to 11 weeks after the initial infection. Serum from animals with a chronic infection of 6-42 months, did not suppress in vitro cell-mediated immunity. The suppressive factor was heat-stable, non-dialysable and, following ultracentrifugation of the suppressive serum, was found to be present in the high mol. wt fraction. From these studies, it is suggested that the immunosuppressive factors are immune complexes, which appear in the serum of the baboons following their infection with this blood parasite.

Topics: Animals; Antigen-Antibody Complex; Cells, Cultured; Concanavalin A; Female; Haplorhini; Immune Tolerance; Kinetics; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Papio; Phytohemagglutinins; Schistosoma mansoni; Schistosomiasis; Ultracentrifugation

Cultures of splenocytes from mice infected with the Formosan and Indonesian strains of Schistosoma japonicum demonstrated a blastogenic response to concanavalin A (Con-A), adult worm antigen (SAA) and soluble egg antigen (SEA). The incorporation of tritiated thymidine was significantly greater for lymphocytes from mice infected with the pathogenic Indonesian strain than for lymphocytes from mice infected with the non-pathogenic Formosan strain in response to SAA; the responses also increased with duration of infection. The response to SEA, however, was only greater for the Indonesian strain, than that for the Formosan strain, at six weeks and the differences in response not statistically significant at five, seven, and nine weeks post-infection. The differences may have been associated with the number of worms developing in the mice since the adult worm recovery for the Indonesian strain was nearly twice that of recoveries from mice infected with the Formosan strain.

Topics: Animals; Antigens; Concanavalin A; Indonesia; Lymphocyte Activation; Mice; Schistosoma japonicum; Schistosomiasis; Taiwan

Topics: Animals; Antigens; Cell Adhesion; Concanavalin A; Epitopes; Immunity, Cellular; Lymphocyte Activation; Phytohemagglutinins; Rats; Schistosoma mansoni; Schistosomiasis; T-Lymphocytes

Antigens of Fasciola hepatica adult worms were chromatographed using concanavalin A-Sepharose 4B. Two unbound peaks appeared in the inclusion volume (DT-1 and DT-2), and one peak was eluted with alpha-methylglucoside (E1-1). At least seven peaks were obtained by isoelectric focusing of E1-1. The largest of these peaks, with an average pI of 4.0, contained the antigens reactive with antibodies to Schistosoma mansoni. Mice immunized with DT-2 or E1-1 and challenged with S. mansoni cercariae developed 39 to 82% fewer worms than controls. DT-1 had no protective effect. Combining DT-1 and DT-2 abolished this protection. These experiments demonstrate that F. hepatica glycoprotein antigens induce in mice significant protection to infection with S. mansoni and offer an interesting approach to the study of vaccines in experimental schistosomiasis.

Topics: Animals; Antigens; Chromatography, Affinity; Concanavalin A; Fasciola hepatica; Immunity; Immunization; Immunodiffusion; Isoelectric Focusing; Mice; Rabbits; Schistosoma mansoni; Schistosomiasis; Sepharose

Analysis of a murine model of schistosomiasis revealed that both the thymus (T)- and bursa (B)-derived compartments of the immune system are modified during acute infection. The functional capacity of T and B lymphocytes to respond to mitogenic stimuli and the humoral response to thymus-dependent (SRBC) and thymus-independent (DNP-Ficoll) antigens are severely depressed. In addition, it was found that suppressor cells capable of inhibiting the response of normal lymphocytes to SRBC arise during acute infection. Although the splenic frequency of T (theta) and B (Ig+) cells remained constant during chronic infection, quantitative changes were detected in each population. In the T cell pool there was a decrease in the percentage of Ly-1+ cells and a concomitant increase in Ly-1+, 2+, 3+, cells, whereas the B cell pool showed a progressive loss of complement receptor-bearing lymphocytes, which apparently was the result of inactivation of surface complement receptor by a serum factor specifically found in infected mice. Characterization of the serum factor strongly suggests it is an immune complex. Thus, it appears that both suppressor cells and immune complexes contribute to changes noted in the immune system during acute schistosomiasis. Additional studies carried out in mice after unisexual infection revealed that egg production is not a necessary prerequisite for several of the immunologic phenomena associated with acute schistosomiasis.

Topics: Animals; B-Lymphocytes; Binding, Competitive; Clone Cells; Concanavalin A; Female; Immunoglobulin M; Immunosuppression Therapy; Lipopolysaccharides; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Schistosoma mansoni; Schistosomiasis; Spleen; T-Lymphocytes

Previous work (1)(1) has shown that normal human eosinophils show a preferential capacity, in comparison with neutrophils, to bind to antibody- coated schistosomula of Schistosoma mansoni. This effect is attributable to a temperature-dependent function of the eosinophil which renders its binding stable and irreversible by aggregated gamma globulin or Staphylococcus aureus protein A. In contrast, the binding of neutrophils is readily reversible by these agents. It has now been shown that the differences observed between eosinophils and neutrophils is a property of their interaction with living schistosomula. When dead or artificially damaged schistosomula were tested, neutrophils showed a markedly enhanced capacity to adhere, in both the presence and absence of anti-chistosomular serum. Subsequent experiments were designed to test the hypothesis that the strong, stable binding of eosinophils was attributable to degranulation, with release of granule contents which would then serve as ligands to bind the cell to the organism. First, an enhanced adherence both of eosinophils and of neutrophils could be demonstrated in the presence of eosinophil major basic protein (MBP) or of protamine, a high molecular weight cation. Second, the binding of eosinophils induced by concanavalin A (Con A) was found to differ markedly from that induced by antischistosomular serum. Con A-mediated binding of eosinophils was fully reversible by alpha-methyl-mannoside, was not associated with damage to the organism, and did not lead to degranulation of the cell, as estimated by measuring the release of MBP into the culture supernate. However, induction of degranulation of concanavalin A-bound eosinophils, but not of neutrophils, with the calcium ionophore A23187 converted the reaction into one which was no longer reversible by alpha- methylmannoside and in which damage to the organism now did occur. These findings support the hypothesis that the stable binding of eosinophils is associated with degranulation, a process which may contribute to the preferential capacity of this cell to mediate antibody-dependent damage to schistosomula.

Topics: Antibodies; Calcimycin; Cell Adhesion; Concanavalin A; Cytoplasmic Granules; Eosinophils; Humans; Immunity, Cellular; Methylmannosides; Neutrophils; Schistosoma mansoni; Schistosomiasis

Spleen cells from normal CBA/J mice or mice infected with Schistosoma mansoni were exposed for 48 to 72 hr to either concanavalin A (Con A), soluble egg antigen (SEA), or soluble worm antigenic preparation (SWAP), treated with mitomycin C to prevent further DNA synthesis, and admixed with either normal or sensitized syngeneic spleen cells exposed to a concentration gradient of phytohemagglutinin (PHA) or SEA, respectively. Both nonspecific (by Con A) and "antigen-specific" (by SEA and SWAP in infected mice only) induction of suppression was observed when using PHA-induced blastogenesis as the final assay. The number of mice with inducible splenic suppressive activity and the degree of PHA suppression induced by exposure to SEA appeared to decline between 8 and 20 weeks of infection. In contrast, when the response of spleen cells from mice infected for 8 weeks to SEA served as the final assay, strong suppressive activity was induced from the spleen cells of all chronically infected mice (20 weeks of infection). This model permits parallel analysis of the induction of suppressor activity by nonspecific and schistosome antigen-specific signals during the course of this chronic, immunoregulated condition, schistosomiasis mansoni.

Topics: Animals; Antigens; Concanavalin A; Female; Immunosuppression Therapy; Lymphocyte Activation; Male; Mice; Mice, Inbred CBA; Ovum; Phytohemagglutinins; Schistosoma mansoni; Schistosomiasis; Solubility; Spleen

Topics: Antigens; Chronic Disease; Concanavalin A; Culture Media; Dose-Response Relationship, Immunologic; Female; Humans; Immunity, Cellular; Immunosuppression Therapy; Lectins; Lymphocyte Activation; Ovum; Schistosoma mansoni; Schistosomiasis

Guinea pigs infected with Schistosoma mansoni were tested for in vitro lymphocyte response to schistosome antigens and nonspecific mitogens at various times after infection. Production of macrophage migration inhibition factor by peritoneal exudate cells in response to cercarial, adult, and egg antigens reached a peak between 4 and 8 weeks post-infection and diminished rapidly thereafter. In contrast, peak blastogenic responses of blood lymphocytes appeared later than 8 weeks for all antigens and persisted until at least the 24th week. Blastogenic responses to concanavalin A and phytohemagglutinin P were not significantly different in normal and infected animals.

Topics: Animals; Antigens; Concanavalin A; Female; Guinea Pigs; Lectins; Lymphocyte Activation; Macrophage Migration-Inhibitory Factors; Macrophages; Ovum; Schistosoma mansoni; Schistosomiasis; Time Factors

The lymphoid cell population responsible for production of eosinophil stimulation promoter (ESP), a lymphokine which increases migration of eosinophils, was investigated in murine Schistosoma mansoni infection. Con A challenge induced ESP production, whereas LPS did not. Prior treatment with anti-thetaC3H alloantiserum plus complement in vitro eliminated ESP production; in vivo treatment with rabbit anti-mouse thymocyte serum consistently reduced ESP production by splenic lymphoid cells, but affected lymph node cell ESP production only after exceptionally large doses. Thymocytes did not produce significant amounts of ESP; nor did lymphoid cells from congenitally athymic mice. Depletion of B lymphocytes and macrophages by nylon fiber adherence eliminated antigen-induced ESP production; this was partially restored by addition of non-immune, 72-hr peritoneal exudate cells. Con A-induced ESP production was not affected by nylon fiber treatment. These results demonstrate that ESP is produced by an ATS-sensitive, peripheralized T lymphocyte population, and suggest a macrophage requirement for antigen-induced production of this lymphokine.

Topics: Animals; Antilymphocyte Serum; Cell Adhesion; Complement System Proteins; Concanavalin A; Eosinophils; Lipopolysaccharides; Lymph Nodes; Lymphokines; Mice; Mice, Inbred AKR; Mice, Inbred CBA; Mice, Inbred Strains; Nylons; Schistosoma mansoni; Schistosomiasis; Spleen; T-Lymphocytes

Chronic murine schistosomiasis mansoni is associated with depressed cell-mediated immune responses to Schistosoma mansoni egg antigens. The present study has examined the possibility that factors develop during infection that are capable of altering the response of lymphocytes to stimuli other than specific schistosomal antigens. Egg production begins at 5 weeks, and 1 to 3 weeks later there is a moderate degree of unresponsiveness of lymph node and spleen cells to the mitogens concanavalin A and phytohemagglutinin. This was associated with an altered dose response curve to the mitogens similar to that observed in antigenic systems. Seven weeks after the initiation of antigenic stimulation (egg prodiction lymph node and spleen cells from chronically infected animals were profoundly unresponsive to all concentrations of concanavalin A and phytohemagglutinin tested. These investigations suggest that, in addition to possible blockade by serum antibody, other suppressive factors may be involved in the spontaneous modulation of immunopathology in chronic schistosomiasis. These are detectable 1 to 3 weeks after the onset of egg production and are prominent at 12 weeks. Such findings are consistent with, but do not prove, the existence of suppressor T cells in chronic schistosomiasis.

Topics: Animals; Antibody-Producing Cells; Chronic Disease; Concanavalin A; DNA; Female; Immunosuppression Therapy; Lectins; Lymph Nodes; Lymphocyte Activation; Mice; Schistosoma mansoni; Schistosomiasis; Spleen; T-Lymphocytes