Search PubMed⌕ Search

Biomedical subjects

C Auriault

Publications and source records attributed to C Auriault.

At least 73 records · Page 4Linked to original sources
PubMed1991

Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. II. Induction of protective immunity in experimental rat schistosomiasis.

In our previous work on the idiotypic network in the rat model of schistosomiasis we showed that immunization with an IgE mAb specific for 26/56-kDa parasitic Ag resulted in the production of anti-anti-Id antibodies of both the IgG and IgE classes. Further studies demonstrated that anti-Ab2 T cell lines, obtained by immunization with Ab2 antibodies, functioned as conventional Th cells; they were MHC-restricted and required APC to proliferate in the presence of the native schistosomula Ag and the Ab2 antibodies. We report the involvement of these anti-Ab2 cells in the regulation of protective immunity. The transfer of long term culture anti-Ab2 T cell lines into LOU/M rats, followed by a challenge infection by Schistosoma mansoni 1 day after the cell transfer led to a slight increase in the worm burden. On the contrary, the transfer of anti-Ab2 T cells 90 days before S. mansoni infection induced a significant reduction of the worm burden (up to 57%). T cells recovered from the protected rats were stimulated by the native schistosomula Ag as well as by tryptic fragments of IgG isolated from the Ab2 sera, in the presence of irradiated thymic cells as APC. We also analyzed the humoral response developed by the rats after transfer with the anti-Ab2 T cell lines. The sera induced various inflammatory cells into cytotoxic effectors against the larvae of S. mansoni, arguing for the presence of functional IgE in the sera. Moreover, when these sera were passively transferred into rats infected 1 day later, a significant reduction of the worm burden was observed. However, antibody-dependent cytotoxic mechanisms efficient 10 days after the anti-Ab2 T cell transfer did not correlate with the protective immunity which required a 90-day delay to be established. These data suggest that the protective immunity induced by the anti-Ab2 cells is supported both by the cellular and humoral components and that in a future vaccinating strategy the idiotypic network may play a crucial role.

Animals↗
PubMed1991

Identification and characterization of a functional receptor for interferon-gamma on a megakaryocytic cell line.

We have previously shown that human interferon-gamma (Hu-IFN-gamma) induces platelets to become efficient effector cells, capable of killing young larvae of the parasite Schistosoma mansoni. Recently, binding sites for IFN-gamma on platelets have been characterized. We show here the presence of high-affinity receptors for IFN-gamma on the surface of the human megakaryocytic Dami cell line. Scatchard analysis indicated the presence of about 11,000 binding sites per cell, with a kd of 3 +/- 0.5 x 10(-10) mol/L; the apparent molecular weight of the receptor was 90 Kd. Receptor-bound 125I Hu-recombinant IFN-gamma was rapidly internalized and degraded when the temperature was increased from 4 degrees C to 37 degrees C. The half-life of this receptor was about 7 hours, and pretreatment of cells with IFN-gamma or phorbol myristate acetate had very little effect on the surface receptor number and no detectable effect on IFN-gamma receptor messenger RNA (mRNA) expression. The receptor was functional, because 24 hours of treatment with IFN-gamma led to the increase of HLA class I mRNA expression and to the initiation of HLA class II mRNA expression. These effects were selective because platelet glycoprotein Ib, IIb, or IIIa mRNA expression and cell proliferation were unaffected.

Blotting, Northern↗
PubMed1991

Antigenicity and immunogenicity of a multiple peptidic construction of the Schistosoma mansoni Sm-28 GST antigen in rat, mouse, and monkey. 1. Partial protection of Fischer rat after active immunization.

Among the schistosome proteins characterized as vaccine candidates, an Ag of 28 kDa (Sm-28-GST) has received considerable attention. It was shown to be antigenic in humans and protective in mice, rats, hamsters, and baboons. Synthetic peptides derived from its sequence have been used to characterize the immune response to the molecule and one of these, comprising aminoacids 115-131 has been shown to incorporate both T and B cell recognition sites in a variety of experimental models. An octameric ("octopus") construction of the 115-131 peptide has been synthesized and its antigenicity and immunogenicity have been examined. The octopus construct is immunogenic in rats, mice and baboons in the presence of CFA (for rodents) and Bacille-Calmette-Guérin vaccine (for primates) as adjuvants. This clearly indicates that the construction allowed the conservation of the immune sites of the cognate protein. Moreover, anti-octopus sera from immunized Fischer rats were able to mediate platelet-, macrophage-, and eosinophil-dependent cytotoxicity toward schistosomula. Rats immunized with the 115-131 octopus were partially protected against a challenge infection with Schistosoma mansoni cercariae and this was paralleled by an increased level of IgG and more importantly, of IgE Sm-28-GST-specific antibodies.

Amino Acid Sequence↗
PubMed1991

Obtention of a human primary humoral response against schistosome protective antigens in severe combined immunodeficiency mice after the transfer of human peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) from healthy donors were injected into C.B.-17 severe combined immunodeficiency (scid) mice which were subsequently immunized with crude Schistosoma mansoni adult worm antigenic preparation (SWAP) or with recombinant S. mansoni 28-kDa glutathione transferase (r-Sm-28-GST) antigen. PBMC from a S. mansoni-infected patient were also transferred. The specific human anti-SWAP and anti-Sm-28-GST antibody responses were monitored. The presence in both cases of human specific antibodies in scid mouse sera was determined by enzyme-linked immunosorbent assay and Western blotting techniques using anti-human immunoglobulin reagents. No antibodies were detected in these sera using anti-mouse immunoglobulin antisera. These antibodies were functional since a cytotoxic activity against schistosomula was observed when monocytes were incubated with scid mouse sera positive for anti-Sm-28-GST antibodies.

Animals↗
PubMed1991

Effect of ubiquitin on platelet functions: possible identity with platelet activity suppressive lymphokine (PASL).

In an attempt to clone a suppressive lymphokine of platelet function (PASL), we have obtained a cDNA clone coding for the previously described human ubiquitin-80 amino acid fusion protein. Our clone differs from the described sequence in that it contains the complete amino acid sequence of ubiquitin as well as a short (25 bp) 5' noncoding region. In addition the 3' untranslated region is slightly longer than that previously shown. Like PASL, purified ubiquitin can inhibit the cytotoxic properties of platelets and the production of oxygen metabolites by these cells. Moreover, this molecule is able to act as a proaggregating factor and seems of a great interest in pathologies involving defects in platelet aggregation. Ubiquitin could also have a potential use in the regulation of immunological disorders in which platelets seem to be implicated such as hymenoptera venom hypersensitivity and aspirin-sensitive asthma, since in both situations, ubiquitin is able, as is PASL, to inhibit the cytotoxic function of platelets. Indeed ubiquitin possesses important pharmacological potentialities which have not been previously described. This molecule and PASL share several similarities in their functional and physicochemical properties. PASL could therefore belong to the family of ubiquitins.

Adenosine Diphosphate↗
PubMed1991

Identification of T cell epitopes within a 23-kD antigen (P24) of Toxoplasma gondii.

Among the potentially vaccinating antigens, the products excreted/secreted by the parasite T. gondii have been demonstrated to be excellent candidates. The molecular cloning of one of these antigens (P24) present in excreted/secreted antigens (ESA) has recently been carried out in our laboratory. The recombinant antigen P24 corresponds to a native molecule of 23 kD. We were interested in determining the main epitopes of the P24 antigen eliciting a T lymphocyte response using synthetic peptides derived from the primary structure of P24. Five peptides: 64-79, 88-109, 170-193, 194-208 and 231-250 were synthesized according to their hydrophobicity, mobility and accessibility profiles. The presence of T lymphocyte epitopes in these peptides has been examined in the rat model. The determination of T cell epitopes was carried out using T lymphocytes from infected rats, and from ESA and P24 expression vaccine virus immunized rats. The results showed that the stimulation of T cells with these peptides varied according to the period after Toxoplasma infection. The main T cell stimulation was obtained with the 88-109, 170-193 and 194-208 peptides. When Fisher rats were immunized with ESA, a most significant stimulation was achieved with the 170-193 and 194-208 peptides. In addition, T lymphocytes primed with P24 expressed vaccine virus immunization were more stimulated with the 88-109 and the 194-208 peptides. This study showed that P24-derived peptide-specific T cells were elicited in the three experimental situations, although no antibody response against the 23-kD native antigen was evidenced in the Fisher rat model. However, the native antigen (presented by irradiated parasites) can induce a proliferative response of the 170-193 peptide-specific T lymphocytes, confirming that this peptide contains an important T cell epitope. The adoptive transfer into athymic rats of T helper cells recovered from 170-193 peptide-immunized Fisher rat conferred a significant protection to infected nude rats despite the fact that no antibody production was observed.

Animals↗
PubMed1991

Platelet cytotoxicity against parasites.

Platelets are not restricted to hemostasis and thrombosis since they are involved in defence mechanisms especially in parasitic diseases. They express cytotoxic functions in vitro and in vivo against extra-cellular and intra-cellular parasites. The toxic process is mediated either by specific antibodies or directly by the parasite itself. As some metabolic pathways seem to be implicated both in hemostasis and in parasiticidal activity, primary hemostasis and cytotoxicity may be considered as specialized inflammatory responses.

Animals↗
PubMed1990

Biological effect of interferon-gamma during the course of experimental infection of rat by Schistosoma mansoni.

We demonstrate here that a second mechanism of platelet activation dependent on lymphokine could also take place in the expression of platelet cytotoxicity against Schistosoma mansoni in vitro. Indeed, IgE, as previously described, but also IFN-gamma, present in the sera of infected rats, together induce platelets from normal rats into cytotoxic effectors for the parasitic larvae. This second mechanism appears also effective in vivo since the passive transfer of normal platelets treated by recombinant IFN-gamma (rIFN-gamma) and the administration of rIFN-gamma to rats conferred a protective immunity to S. mansoni.

Animals↗
PubMed1990

The neuropeptide substance P stimulates the effector functions of platelets.

Sensory neuropeptides, such as substance P, appear as potent mediators of various immunological reactions, and inhibit or stimulate a wide range of functions of immune inflammatory cells. Platelets were recently shown to participate as effector cells in an IgE or lymphokine-dependent killing of parasites. Substance P and its carboxy-terminal fragment SP (4-11) induce the cytotoxic activity of platelets towards the larvae of Schistosoma mansoni, respectively, by 90% and 40%, whereas the modified C terminal SP, the SP-free acid, exhibits no effect on the platelets. The neuropeptide effects occur at low doses (10(-8) M), are specific as shown by inhibition studies with a substance P antagonist, the D-SP. Binding data obtained after flow cytofluorometry with FITC-SP lead to the conclusion that SP binds specifically to about 20% of the homogenous population of platelets. Moreover, IgE could modulate the SP-dependent functions of platelets since the pre-incubation with myeloma human IgE or with AP2 monoclonal antibodies--known to inhibit the IgE-dependent killing of these cells-leads to a dramatic decrease of the SP dependent cytotoxic activity of platelets towards the larvae. These findings identify a potent mechanism for nervous system regulation of host defence responses.

Amino Acid Sequence↗
PubMed1990

Protection of nude rats against Toxoplasma infection by excreted-secreted antigen-specific helper T cells.

In the present work we demonstrate the implication of excreted-secreted antigens in eliciting the protective cell-mediated immunity developed by rats toward Toxoplasma gondii. We first showed that 10(4) specific T cells from T. gondii-infected rats conferred to nude rats the ability to resist an infection by the highly virulent RH strain of T. gondii. In a second series of experiments, the role of excreted-secreted antigens in this protection was demonstrated. After the adoptive transfer to nude rats of various doses (10(3), 10(4), 10(5)) of excreted-secreted antigen-specific helper T cells (propagated in vitro during one month), significant protection toward T. gondii was induced. Moreover, these cells were responsible for a specific antibody response in nude rats, which are normally unable to develop any specific humoral response. The specificity of these antibodies was directed toward different molecules with molecular masses of 104, 97, 57, 39, 30, 21, and 18 kilodaltons; some of these have been previously characterized as major excreted-secreted antigens.

Animals↗
PubMed1990

Antibody response of Schistosoma mansoni-infected human subjects to the recombinant P28 glutathione-S-transferase and to synthetic peptides.

The 28-kilodalton antigen of Schistosoma mansoni has been previously described as having importance as the basis for a potential vaccine. The P28 recombinant molecule and three peptides derived from its primary sequence, namely the 24-43, 115-131, and 140-153 peptides, have been tested to evaluate the humoral responses of Kenyan school children previously classified as susceptible or resistant to reinfection after chemotherapy. We report here that the P28 molecule and two of the peptides studied (peptides 115-131 and 140-153) can be used for detecting specific immunoglobulin G (IgG), IgE, and IgA antibodies. Moreover, the IgG4 response of the susceptible population was significantly greater than that of the resistant group, whereas no differences between the two populations were noticed in total IgG anti-P28 antibodies. This suggested that IgG4 could play a role in the lack of immunity of susceptible patients. A strong IgG3 response restricted to the 140-153 peptide was observed but did not discriminate between the resistant and susceptible populations. In contrast, a marked increase in the IgA response to the 140-153 peptide epitope(s) in sera of the resistant population was noticed. Taken together, these results suggest that the P28 antigen and two of the three peptides selected could give predictive information about the development of the disease or the efficiency of vaccination with P28 as the immunogen.

Adolescent↗
PubMed1990

Protection of rats against Schistosoma mansoni infection induced by platelets stimulated with the murine recombinant tumor necrosis factor alpha.

Human recombinant tumor necrosis factor (rTNF alpha) and lymphotoxin (rTNF beta) have been shown to enhance the schistosomicidal activity of human platelets in vitro. In this report, we demonstrated that the murine rTNF was able to induce the in vitro cytotoxic activity of both murine and rat platelets towards the larvae of Schistosoma mansoni, whereas human rTNFs activated only the murine platelets. Passive transfer of platelets stimulated with murine rTNF significantly protected rats up to a 65% reduction of the worm burden. Thus, rTNF may constitute, via its interactions with effector cells, an important regulatory mechanism during the parasitic infection of rats.

Animals↗
PubMed1990

T-cell responsiveness towards various synthetic peptides of the P28 antigen in rat and mouse models during Schistosoma mansoni infection.

It has recently been demonstrated that the Schistosoma mansoni P28 antigen can induce a strong protective immunity after direct immunization in various experimental models. T lymphocytes from Fischer rats immunized with the recombinant P28 antigen were cultured in vitro in the presence of seven synthetic peptides derived from the amino acid sequence of the P28. The most significant and reproducible proliferation was obtained with the 24-43 and 115-131 synthetic peptides. In order to analyze whether these located determinants were also exposed to the host's immune system during the natural S. mansoni infection or after immunization with crude antigenic extracts of various development stages of the parasite, the T-cell responsiveness of infected or immunized Fischer rats and BALB/c mice was tested towards these synthetic peptides. The results showed that, in both permissive (mouse) and non-permissive (rat) hosts, 24-43 and 115-131 synthetic peptides are recognized during the course of infection and that there is a dynamic variation of this recognition. These peptides are also recognized by T cells educated against crude antigenic extracts of different developmental stages of the parasite which contained the native form of the P28 molecule. Taken together, the results indicated that these synthetic peptides derived from the recombinant P28 antigen can activate T lymphocytes educated against the native P28 molecule during the development and maturation of the parasite in their hosts. Therefore, they might be useful for the construction of synthetic vaccines against schistosomiasis.

Amino Acid Sequence↗
PubMed1989

Protective immunity in mice vaccinated with the Schistosoma mansoni P-28-1 antigen.

The P28-1 Ag induces a strong protective immunity toward Schistosoma mansoni infection in various experimental models. T lymphocytes of mice immunized with the recombinant P28-1 Ag were stimulated in vitro by schistosome Ag of different development stages and by three P28-1 Ag-derived synthetic peptides. The most significant stimulation was achieved with the 24-43 peptide. The use of two fragments of this peptide showed that the P28-1 T lymphocyte specificity concerned essentially the NH2 terminal sequence of the 24-43 peptide. Moreover, T lymphocytes specific for the 24-43 peptide were stimulated by both schistosome Ag and the recombinant P28-1 protein. The passive transfer of (Th + Ts) lymphocytes recovered from P28-1 Ag-immunized mice increased the IgG response to P28-1 and its peptides during infection but did not protect against a challenge infection, such as the passive transfer of anti-P28-1 sera. In contrast, P28-1 specific Th cell lines maintained in culture for 2 mo, passively transferred a strong protection (50%) to infected mice. Supernatants of P28-1-specific T cells obtained after stimulation with the corresponding Ag, were able to confer cytotoxic properties to platelets and macrophages. The presence of IFN-gamma for the cytotoxicity mediated by platelets and macrophage activating factor for the cytotoxicity mediated by macrophages in these supernatants is in a large part responsible for the parasite killing observed. Finally, a preliminary immunogenetic approach with H-2 congenic mice on BALB background showed that the P28-1 Ag T cell response was under the control of the MHC and that the H-2b haplotype determined a low response to P28-1 Ag and its peptides while H-2d and k haplotypes determined high responders.

Animals↗
PubMed1989

In vitro and in vivo effects of interleukin 2 on the protozoan parasite leishmania.

T cells can have either resistance-promoting or disease-promoting effects in murine cutaneous leishmaniasis. It is known that the adoptive transfer of parasite-specific helper T cells led to an exacerbation of Leishmania-induced lesions. This work presents evidence that lymphokines produced by activated T cells could be involved in this exacerbating process by directly stimulating the parasite growth. In the presence of activated T cell supernatants, the in vitro growth of Leishmania mexicana amazonensis promastigotes was greatly enhanced. This effect was reproduced by addition of recombinant interleukin 2 (IL2). An anti-IL2 antibody partially reversed the stimulatory effect of IL. An in vivo in situ treatment of infected mice with IL 2 led to an exacerbation of the lesions. The increase in footpad swelling after IL2 treatment was correlated with a higher number of parasites per lesion. The protective effect of cyclosporin A against the development of Leishmania infection was abolished by IL2 treatment. As we observed that IL2 has a stimulatory effect on the in vitro Leishmania growth, we speculate that exacerbation of the lesions observed in vivo after IL2 treatment could be partially related with a direct effect of IL2 on the parasite growth.

Animals↗
PubMed1989

[Antigens of Toxoplasma gondii with a diagnostic and potential immunoprophylactic value: new strategies of identification].

Toxoplasma gondii is an ubiquitous protozoan parasite which induces severe pathology in in utero infected children and in immunosuppressed patients (particularly in the case of AIDS). Previous work that focused on toxoplasma somatic antigens failed to demonstrate an efficient protection against highly virulent T. gondii strains. The authors therefore first studied the role of parasite excreted-secreted (ES) antigens in the immune response. They describe here the preparation of excreted-secreted antigens in cell-free medium from tachyzoites, the intracellular proliferative stage present during acute infection. Major ES antigens have Mr of 108 K, 97 K, 86 K, 57 K, 42 K, 39 K, 28.5 K, 27 K and 21 K. The protective role of ES antigens has been demonstrated using congenitally athymic (Nu/Nu) rats that are highly sensitive to T. gondii infection (+/+ Fischer rats are resistant). The humoral and cellular components of this protection have been studied by the passive transfer either of sera or of T lymphocytes from ES-immunized +/+ Fischer rats into Nu/Nu rats. Adoptive transfers were carried out 24 hours before infection with the highly virulent T. gondii RH strain. Based on the concept of concomitant immunity, the authors have characterized antigens from tachyzoites and bradyzoites (the encysted stage persisting during chronic infection) which share common epitopes. Four tachyzoite antigens, P63, GP43, P39 and GP 28.5 have been shown by immunoprecipitation to cross-react with bradyzoite antigens. Two monoclonal antibodies raised against ES antigens permitted to demonstrate the localization of the 28.5 K and 27 K antigens inside the dense granules of tachyzoites and bradyzoites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Human recombinant gamma-interferon stimulates proliferation and inhibits collagen and fibronectin production by human dental pulp fibroblasts.

Human recombinant-gamma-interferon was tested on human dental pulp fibroblast activity in vitro. Fibroblast proliferation was estimated by a colorimetric test. Type I and type III collagens and fibronectin were quantified by radioimmunoassay in culture supernatant from confluent fibroblasts. A dose dependent stimulation of the proliferation was observed when fibroblasts were treated with recombinant-gamma-interferon. In contrast, an inhibition of the synthesis of soluble types I and III collagen and fibronectin by confluent cell cultures treated with recombinant-gamma-interferon occurred without apparent modification of the insoluble collagen level in the cell layer. Quantimetric analysis of type I collagen immunoperoxidase labelling have demonstrated that there was no intracellular storage of type I collagen in these cultured fibroblasts. These data support the view that human recombinant-gamma-interferon can affect human dental pulp fibroblast functions and thus may play an important part in the regulation of fibrosis.

Cell Division↗