Biomedical subjects

C Auriault

Publications and source records attributed to C Auriault.

At least 91 records · Page 5Linked to original sources

PubMed1989

Characterization of a suppressive factor of platelet cytotoxic functions in human and rat schistosomiasis mansoni.

In a previous study we demonstrated that mitogen-stimulated CD8+ CD4-T cells from normal donors produce a suppressive lymphokine (PASL) of IgE-dependent platelet cytotoxicity. Here we demonstrate the production, after antigenic-stimulation, of this suppressive factor during ongoing infections by Schistosoma mansoni in man and in the rat. The T lymphocyte subpopulation producing this factor was also identified as expressing the marker of the suppressive subset. Because of the absence of species restriction, the relevance in vivo of PASL was determined in the rat model. In these conditions we observed a complete abolition of the protection normally conferred against a challenge infection by the passive transfer of platelets from immune to normal rats after treatment of transferred platelets with T lymphocyte supernatants.

Animals↗

PubMed1988

Analysis of T and B cell epitopes of the Schistosoma mansoni P28 antigen in the rat model by using synthetic peptides.

The Schistosoma mansoni P28 molecule is an Ag inducing protective immunity in various experimental models. Three synthetic peptides, derived from the primary sequence of the recombinant P28 and comprising amino acids 24-43, 115-131, and 140-153, respectively, were synthesized according to their hydrophilicity, mobility, and accessibility profiles. The presence of B and T lymphocyte epitopes in these peptides has been examined in the rat model. The results showed that the 24-43 and the 115-131 peptides contained major epitopes for IgG but not for IgE. Moreover, the 24-43 peptide-specific IgG produced after injecting either the recombinant P28 Ag or the 24-43 peptide coupled to tetanus toxoid was essentially of the IgG2a subclass and to a lesser extent of the IgG1 subclass, whereas no IgG2c was detected. These 24-43 peptide-specific antibodies were cytotoxic in vitro for schistosomula in the presence of eosinophils as effector cells. The 24-43 and the 140-153 peptides contained major targets of T lymphocytes specific for the recombinant P28 Ag. T cell lines specific for the 24-43 peptide have been prepared. These cells proliferated in vitro when stimulated with various S. mansoni crude antigenic preparations or with the recombinant P28 Ag. Moreover, their passive transfer to rats immunized with the P28 Ag led to a significant increase in specific IgE without modifying the IgG response.

Animals↗

PubMed1988

Protective role of IgE in immunocompromised rat toxoplasmosis.

In contrast to euthymic adult Fischer rats, immunocompromised Nu/Nu animals develop a lethal infection when inoculated with the RH strain of the protozoan Toxoplasma gondii. However, a significant period of survival is obtained when Nu/Nu rats are passively transferred with sera from 28-day infected Fischer +/+ (euthymic) animals. Specific IgE are involved since IgE-depleted sera are unable to afford such a protection. Only excreted/secreted Ag or living tachyzoites are able to induce a significant protective IgE response in intact animals. In addition, platelets or, to a lesser extent, eosinophil-rich populations from Toxoplasma infected or excreted-secreted Ag-immunized euthymic animals bear surface IgE and are cytotoxic for the parasite in vitro. Also, adoptive transfer of immune platelets confers a significant degree of protection to Toxoplasma-infected Nu/Nu animals. Our results clearly show the key role of Ag present in both living parasites and excreted-secreted Ag to induce, in this model, a protective IgE response. In addition, as in other parasitic infections, platelets and probably eosinophils are the effector cells involved in controlling parasitic dissemination during Toxoplasma infection in immunocompromised rats.

Animals↗

PubMed1988

Recombinant tumor necrosis factors mediate platelet cytotoxicity to Schistosoma mansoni larvae.

The involvement of platelets in the immunity directed toward the parasite Schistosoma mansoni has been demonstrated in vitro and in vivo. The killing properties of platelets were shown previously to involve specific IgE after their binding to a membrane receptor. More recently, we have demonstrated that lymphokines released by S. mansoni Ag- or lectin-stimulated CD4+/CD8-T cells were able to induce the platelet cytotoxicity. The isoelectric focusing of the T lymphocyte supernatants showed that two factors were able to stimulate the platelet killing functions. One of them was clearly identified as being IFN-gamma. The present work demonstrates that the second lymphokine was TNF. Indeed the rTNF-beta and, to a lesser extent, rTNF-alpha, induce normal platelets into killer cells for the young larvae of schistosome. Moreover, an additive effect of the TNF-alpha and IFN-gamma has been observed.

Adult↗

PubMed1988

Recombinant human interferon-gamma induces increased IgE receptor expression on human platelets.

Human recombinant interferon-gamma (IFN-gamma) significantly increased the expression of receptors for IgE (Fc epsilon RII) on blood platelets. Fc epsilon RII was measured by specific binding of 125I-labeled IgE or flow cytometry experiments. Scatchard analysis of 125I-labeled IgE binding curves revealed that treatment with IFN-gamma increased the number of Fc epsilon RII but did not change the value of the association constant of Fc epsilon RII for 125I-labeled IgE. IFN-alpha had no effect on the expression or affinity of Fc epsilon RII. In addition to Fc epsilon RII, IFN-gamma also modified the expression of the glycoprotein IIb-IIIa complex on the platelet membrane.

Blood Platelets↗

PubMed1988

Induction of a protective antibody-dependent response against toxoplasmosis by in vitro excreted/secreted antigens from tachyzoites of Toxoplasma gondii.

Toxoplasma gondii is a worldwide protozoan parasite which causes severe disease in congenitally infected children and in immunocompromised patients. Besides the well-defined cytoplasmic and membrane antigens of tachyzoites, we felt that excreted/secreted antigens could play a major role in the immune response. We first report the development of a well-controlled procedure for obtaining tachyzoite excreted/secreted antigens (E/SA) in cell-free incubation media. The E/SA immunogenic in human, rat and mouse toxoplasmosis were then characterized. The major E/SA recognized by human sera from the chronic phase of toxoplasmosis had molecular weights of 108, 97, 86, 69, 60, 57, 42, 39, 28.5, 27 and 26 kD. When injected into +/+ Fischer rats, E/SA elicited high antibody titres. In addition, passive transfer of these sera to highly susceptible nu/nu littermates induced a significant degree of protection towards the virulent RH strain of T. gondii. This work, which demonstrates the key role played by E/SA in the protective immune response, suggests that these antigens should be of value both for diagnostic purposes and for the development of new strategies for immunization against toxoplasmosis.

Animals↗

PubMed1988

Properties of serine proteases of Schistosoma mansoni schistosomula involved in the regulation of IgE synthesis.

The regulation of IgE synthesis in vitro and in vivo by schistosomula-released products (SRP) has been shown to be dependent on the presence of serine proteases. The present paper concerns the characterization of the enzymes involved. The labelling of SRP with [3H]diisopropyl phosphofluoridate revealed two molecules, one major with an MW of 27,500 and one minor with an MW of 29,000. The same pattern was obtained by labelling of schistosomula or cercariae surfaces as well as of the total schistosomulum homogenate. The properties of these enzymes were studied by means of various specific substrates or inhibitors of serine proteases. The specificity was relatively narrow, but had some similarity with trypsin. When added to lymphoid rat cells in culture, SRP induced an increased expression of receptors for the Fc fragment of IgE (Fc epsilon RII). This suggests that the IgE-enhancing property of SRP was due to serine protease activity which may act by enhancing the lymphocyte Fc epsilon RII.

Animals↗

PubMed1988

IgE-dependent killing of Brugia malayi microfilariae by human platelets and its modulation by T cell products.

Platelets isolated from patients infected with filariasis were cytotoxic for microfilariae in vitro. Moreover, platelets from normal donors acquired killing properties in the presence of serum from infected individuals. The humoral factor involved in this cytotoxic process was shown to be IgE. This IgE-dependent cytotoxicity of platelets was strongly inhibited by antigen-stimulated T lymphocyte supernatants from filarial patients.

Animals↗

PubMed1988

IgE-dependent killing of Schistosoma mansoni schistosomula by human platelets: modulation by T cell products.

The in vitro stimulation of T lymphocytes is known to induce the release of factors that possess distinct biological activities. In the present report, we describe the presence, in supernatants of Schistosoma mansoni antigen stimulated T cells from S. mansoni infected patients, of a factor able to inhibit the IgE-dependent platelet cytotoxicity of the same individuals toward the young larvae of S. mansoni.

Animals↗

PubMed1987

Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni.

A rat monoclonal antibody of IgE isotype (B48-14) raised against Schistosoma mansoni has been generated by the fusion of mesenteric lymph node cells from LOU/M rats immunized with a preparation of adult schistosome worms and IR973F nonsecreting rat myeloma cells. Investigation of the in vitro effector functions of this IgE antibody showed a high level of cytotoxicity against S. mansoni schistosomula in the presence of eosinophils, macrophages, and platelets. A significant level of protection (40 to 60%) against a challenge infection with S. mansoni cercariae was achieved by passive transfer experiment of B48-14 IgE to naive recipient rats. By immunoprecipitation, B48-14 IgE antibodies were shown to react with an antigen of 26 kDa present in excretion-secretion products of schistosomula, previously described as a potential immunogen eliciting a protective IgE response against schistosomiasis.

Animals↗

PubMed1987

Induction of platelet cytotoxic functions by lymphokines: role of interferon-gamma.

Antigen- or mitogen-stimulated CD4+/CD- lymphocytes produced factors able to induce normal human platelets into cytotoxic effectors toward the young larvae of Schistosoma mansoni. The neutralization by monoclonal anti-IFN-gamma antibody of the induction of the platelet killer effect, the presence of IFN-gamma in the CD4+/CD8- lymphocyte supernatant, and, finally, the direct inducer effect of recombinant IFN-gamma clearly demonstrated that IFN-gamma was one of the factors responsible for the induction of platelet cytotoxic functions.

Adult↗

PubMed1987

Differential effect of cyclosporin A (CyA) on IgE response: role of CyA-induced suppressor cells.

Administration of cyclosporin A (CyA, 30 mg/kg) for the five days following immunization of Brown Norway rats with DNP14-OVA in alum abolished the primary total and specific IgE response, whereas this treatment had no significant effect on the secondary IgE response. On the contrary, with a single injection of CyA on the day of priming, the secondary IgE response only is abolished. The inhibition of the secondary IgE response could be attributed to the induction by a single dose of CyA of nylon wool-adherent spleen cells, as shown by passive transfer experiments. CyA might thus affect the IgE response variously depending on single or repeated administrations.

Animals↗

PubMed1987

Helper T cells induced by a purified 28-kilodalton antigen of Schistosoma mansoni protect rats against infection.

Schistosoma mansoni adult worm 28-kilodalton (kDa) proteins were separated on polyacrylamide slab gels, recovered by electrophoretic elution, and used to immunize Fischer rats. After the second or third injection, inguinal lymph node T lymphocytes were propagated in vitro for 4 weeks in the presence of syngeneic antigen-presenting cells and adult worm antigens in medium containing interleukin-2. After this period of culture, 99% of the cells expressed the W3/13+ surface phenotype and 93% of the cells expressed the W3/25+ surface phenotype. These cells were then tested for their in vivo functional activity after transfer to Fischer rats that had been either infected with S. mansoni cercariae or immunized with the 28-kDa purified protein. In each case, an increase of S. mansoni-specific antibodies was observed. Whereas anti-28-kDa antibodies were only detectable at day 40 postinfection in controls injected with normal T lymphocytes, they appeared as early as day 13 postinfection when the animals received 28-kDa protein-specific T lymphocytes. This led to an effective protection of infected rats (45 to 85%) which correlated with the increase in S. mansoni-specific antibodies. These results therefore demonstrate that the 28-kDa protein possesses epitopes capable of activating helper T cells, which confer a strong protective immunity by enhancing the production of cytotoxic antibodies. The stimulation of the 28-kDa-specific T cells with recombinant proteins suggests that the major epitopes are located toward the carboxylic end of the molecule.

Animals↗

PubMed1987

Platelets as effectors in immune and hypersensitivity reactions.

IgE receptors have been recently characterized on human blood platelets. These receptors share common properties within the Fc epsilon R2 previously described on macrophages and eosinophils with a Ka of 3 X 10(7) M-1 and a mean number of 600-1,000 binding sites for IgE per platelet. The production of an anti-Fc epsilon R2 monoclonal antibody has allowed the identification on platelet membrane preparations of two major bands of 43-45 and 31 kD. In parasitic infections (schistosomiasis, filariasis) IgE-dependent killing by platelets has been demonstrated. In allergic asthma and in Hymenoptera venom sensitivity patients, IgE-dependent activation of platelets expressed by the release of cytocidal mediators and oxidative burst can be specifically triggered by the corresponding allergen. In aspirin-sensitive asthma, a direct, non-IgE-dependent platelet activation by nonsteroidal anti-inflammatory drugs has been demonstrated. The platelet abnormality apparently involved a defect of the prostaglandin H2 binding to its specific receptor and a possible imbalance in the regulatory functions of the lipoxygenase metabolites. Platelet effector functions have been recently shown to be regulated by T cell factors. A novel suppressive lymphokine (PASL) produced by OKT8 T cell subset inhibits platelet activation and killing whereas IFN-gamma has been identified among T cell factors produced by OKT4+ cells able to trigger platelet activation. These observations open original perspectives into the pathogenesis, the diagnosis and the prevention of allergic and pseudoallergic disorders, and they provide support to the concept of a role for platelets in various immune and hypersensitivity reactions.

Animals↗

PubMed1987

GP38, P28-I and P28-II: candidates for a vaccine against schistosomiasis.

Three antigens protective against Schistosoma mansoni have been extensively characterized. The schistosomulum surface antigen GP38 possesses an immunodominant carbohydrate epitope of which the structure has been defined. Protection can be achieved via the transfer of monoclonal antibodies recognizing the epitope or by immunization with anti-idiotype monoclonal antibodies. The glycan epitope is shared with the intermediate host, Biomphalaria glabrata as well as being present on other molluscs, including the Keyhole Limpet. A group of molecules at 28 kDa were initially characterized in adult worms and shown to protect rats and mice against a challenge infection. One of these molecules, P28-I, was cloned and expressed in E. coli, yeast and vaccinia virus. The recombinant antigen significantly protected rats, hamsters and baboons against a challenge infection. P28-I is a glutathione-S-transferase and the recombinant antigen produced in yeast exhibits the enzyme activity and has been purified to homogeneity by affinity chromatography. A second P28 antigen, P28-II, has also been cloned, fully sequenced and expressed. This recombinant antigen also protects against S. mansoni infection.

Animals↗

PubMed1987

Regulation of IgE synthesis by macrophages expressing FcE-receptors: role of interleukin 1.

Triggering rat macrophages with IgE complexes induced the production of interleukin 1-like activity (IL-1). The signal is delivered through the macrophage FcE receptor since stimulating macrophages with IgE bound to spleen cells (to avoid endocytosis) or with an anti-FcE receptor antibody linked to nonphagocytizable cells also led to IL-1 production. The molecular weight of IL-1 produced after IgE triggering is in the same range (30 kD) as previously described for rat IL-1. A positive feed-back effect of IL-1 on IgE response was suggested, as purified IL-1 was able to enhance IgE synthesis in vitro by lymphocytes from immunized animals.

Animals↗

PubMed1987

[Infection of the athymic rat by Toxoplasma gondii].

In contrast to normal rats which are resistant to T. gondii infection (10(7) tachyzoïtes), athymic rats did not survive an intraperitoneal infection with 10(3) toxoplasma. When nude rats were injected intravenously with lymph node cells from hirsute littermates, they became resistant in a dose-dependent manner to the infection. In addition, reconstituted athymic rats having survived for more than 4 months the first infection were also protected against a second challenge with 10(5) tachyzoïtes. Anti-T. gondii antibody levels detected in reconstituted athymic rats were related to protection. These preliminary findings suggest that T-dependent immunity is essential in the development of effector mechanisms involving antibodies in resistance to toxoplasmosis.

Animals↗

PubMed1987

Generation and functional analysis of T cell lines and clones specific for schistosomula released products (SRP-A).

Antigens present in the products released by the larval stage of schistosome (SRP-A) were shown to induce a strong cytotoxic and protective IgE response both in the rat and the monkey. T cell lines and clones specific for SRP-A or 26 kD antigens which are the main target of the cytotoxic IgE have been derived. The passive transfer of SRP-A specific T lymphocytes into infected rats led to an increase of the IgE response, conferring a significant level of protection to the rats. In coculture assays in vitro, these cell lines significantly enhanced the production of IgE by SRP-A sensitized rat spleen cells. This helper effect on the IgE response was confirmed with 26 kD T cell clone supernatants. Moreover, supernatants obtained after stimulation with phorbol myristate acetate were able to enhance the IgE production of a hybridoma B cell line (B48-14) producing a monoclonal IgE antibody, cytotoxic for the schistosomula.

Animals↗