[The potential of European research: evaluation and perspectives].
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Developing Countries↗
Biomedical subjects
A Capron
Publications and source records attributed to A Capron.
From protective immunity to allergy: the cellular partners of IgE.
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Animals↗
Hymenolepis diminuta: intestinal mast cell and eosinophil response of the mouse to infection.
It has been demonstrated that the rejection of Hymenolepis diminuta by the mouse is characterized by a humoral response in serum and intestinal lavage. Now the response is also shown to be accompanied by a mast cell and eosinophil response in the lamina propria of the intestine. The mast cell response is, in time and place, correlated with the rejection process of H. diminuta. With regard to the number of eosinophils in the lamina propria, a significant response was only found in the second half of the intestine. The eosinophil peroxidase (EPO) concentration in the intestinal lumen is correlated with the rejection of the parasite and illustrates the involvement of eosinophils in the rejection process. The course of the EPO response is identical to the mast cell response. This, together with other results, suggests that, as to other "systemic" worm infections, a mast cell-eosinophil response may be, at least in part, responsible for the rejection of H. diminuta from the intestinal lumen.
Animals↗
Use of monoclonal antibodies for the characterization of Onchocerca volvulus antigens.
In order to identify Onchocerca volvulus antigens that could be considered as either diagnostic and/or immunoprophylactic, mouse monoclonal antibodies were produced against O. volvulus soluble antigens. Three were selected on the basis of their staining patterns in an indirect fluorescent antibody assay carried out on cryosections of adult O. volvulus. The first monoclonal antibody (K1-159) recognized a cuticular antigen which appeared in IFA to be restricted to the genus Onchocerca. However, neither Western blotting, nor the immunoprecipitation experiments performed on radiolabelled O. volvulus soluble antigen allowed detection of the corresponding antigen(s). The second monoclonal antibody (K1-126) bound to the muscle cells of adults. A 30,000 Mr antigen was detected by Western blot analysis of adult O. volvulus homogenate. This antigen was also recognised by sera from infected patients and corresponding antigenic determinants were detected in extracts of O. gutturosa, Acanthocheilonema viteae and Ascaris suum, but not in Brugia malayi. The third monoclonal antibody (K1-143) recognized egg shells and the surface of adult worms. The target epitope was not species specific and could be found in O. gutturosa, A. viteae, B. malayi and A. suum. The electrophoretic analysis of I-125 labelled soluble antigens and radiolabelled surface antigens of adult O. volvulus, showed numerous antigens (molecular weights ranging from 30,000 to 120,000 Mr) precipitated by K1-143. In an inhibition radioimmunoassay, K1-143 allowed the detection of corresponding antibodies in 79% of the O. volvulus patient sera tested.
Animals↗
IgE receptor on human eosinophils (FcERII). Comparison with B cell CD23 and association with an adhesion molecule.
IgE FcR (FcERII) on human eosinophils was characterized and compared with FcERII present on B cells (CD23). Two mAb, BB10 (anti-eosinophil FcERII) and 135 (anti-CD23), bound to the major component of FcERII at 45,000 to 50,000 Mr, both on purified hypodense eosinophils and on a B cell line (WIL-2WT). The specific ligand, human myeloma IgE, was able to bind to the molecules immunoprecipitated by BB10. A cross-reactivity between BB10 and a mAb anti-Leishmania gp63, which is a "fibronectin (Fn)-like" molecule, containing the L-arginine-L-glycyl-L-aspartyl (RGD) cell attachment domain indicated the presence of such a sequence in the common structure present on eosinophil and B cell FcERII. The synthetic tetrapeptide RGDS as well as its inverted sequence (SDGR) reduced the binding of BB10 and anti-Fn mAb to eosinophils and B cells. Flow microfluorometry analysis revealed a variable binding of BB10 and anti-Fn mAb to eosinophils purified from different patients, results compatible with recent findings on the inducibility of FcERIIb. The significant inhibition of IgE-dependent cytotoxicity against parasite targets by preincubation of eosinophils with BB10, anti-Fn and anti-CD23 mAb, with anti-RGDS polyclonal antibodies or with the SDGR peptide suggested the requirement of this cell adhesion sequence for the function of low affinity FcERII. The presence of such a sequence in the C-terminal domain of B cell FcERII raised the possibility of its role in B cell adhesion or B cell growth.
Amino Acid Sequence↗
Variations in protein expression related to human eosinophil heterogeneity.
In hypereosinophilic patients, eosinophil heterogeneity has been assessed mainly according to morphologic and biologic criteria. In order to investigate the molecular basis of such heterogeneity, biochemical analysis was performed on various eosinophil subpopulations fractionated on metrizamide gradients. Whole cell extracts from purified eosinophils disrupted with a nonionic (NP-40) detergent were successively analyzed by SDS-PAGE and two-dimensional electrophoresis (isoelectric focusing or nonequilibrium pH gradient electrophoresis in the first dimension). Hypodense eosinophils that sediment in the lightest density gradients (18 to 22% metrizamide solution) differed from other purified eosinophils (intermediate and normodense eosinophils respectively collected in 22 to 23% and 23 to 25% metrizamide solutions). Comparative analysis of protein patterns on both monodimensional and bidimensional electrophoresis showed that a basic protein of Mr 51 kDa, present on normodense or intermediate eosinophils, was poorly detected in the case of hypodense eosinophils. In contrast, two other proteins with apparent Mr of about 23 kDa and 41 kDa were exclusively or predominantly identified in these latter cell fractions. Immunochemical analysis with polyclonal antibodies against eosinophil basic proteins and enzymatic assays revealed that the 51-kDa polypeptide could be related to an eosinophil peroxidase-like molecule. In addition, the two proteins detected only in hypodense eosinophils might be related to proteins newly synthesized by in vivo activated eosinophils. Our results suggest that variations in protein expression might represent a good marker of in vivo activation.
Blood Proteins↗
Functional role of human IgG subclasses in eosinophil-mediated killing of schistosomula of Schistosoma mansoni.
Although IgG antibodies and eosinophils have been shown to kill schistosomula of Schistosoma mansoni in vitro, very little data exist that describe the role of each IgG antibody isotype in this event. This study was designed to test the role of each IgG subclass in the eosinophil-dependent killing reaction. IgG antibodies purified by protein G or protein A affinity chromatography demonstrated a killing effect only in the presence of eosinophils activated in vivo or normal eosinophils activated in vitro by eosinophil activating factor. Purification of each IgG isotype allowed confirmation of these results and demonstrated that the killing effect was associated with IgG1 and IgG3 antibodies. IgG2 antibodies expressed a dual function: 1) an effector function with activated eosinophils and 2) a blocking function with normal eosinophils. IgG4 antibodies, whatever the source of eosinophils, blocked the killing mediated by IgG effector antibodies. These findings are discussed in relation to immunity and susceptibility to reinfection in human schistosomiasis.
Adjuvants, Immunologic↗
A circulating suppressive factor of platelet cytotoxic functions after rush immunotherapy in Hymenoptera venom hypersensitivity.
A receptor for the Fc fragment of IgE has been described on human blood platelets. This receptor mediated the IgE-dependent stimulation of platelets by the specific allergen in Hymenoptera venom (HV) hypersensitivity. This platelet reactivity was abolished after rush desensitization. To understand the mechanism of such a down-regulation, we studied the effects of sera recovered from patients treated by HV rush desensitization on platelets of untreated HV sensitive patients. The present data describe the presence of a circulating factor able to suppress, in a dose-dependent manner, platelet stimulation by the specific allergen. This circulating factor was not allergen specific, not depleted by IgE or IgG antibody immunoadsorption, and was found at higher concentrations in the sera of patients receiving monthly high dosages of HV (200 micrograms maintenance dose). The physicochemical characterization showed that this circulating factor had a m.w. of 20,000 to 25,000, an isoelectric point of 4.2, was heat and acid stable, and sensitive to trypsin, but not to neuraminidase. These characteristics were similar to a newly described lymphokine, platelet activity suppressive lymphokine, suggesting the intervention of such a lymphokine in HV rush desensitization.
Bee Venoms↗
Protective effects of anti-antiidiotypic IgE antibodies obtained from an IgE monoclonal antibody specific for a 26-kilodalton Schistosoma mansoni antigen.
A rat IgE mAb specific for larval Ag (26 kDa, 56 kDa) has been shown to protect rats against Schistosoma mansoni infection. Immunizations of Lou/M rats performed with this IgE (Ab1) induced the production of antiidiotypic antibodies (Ab2). Moreover, after this Ab2 production, anti-antiidiotypic antibodies (Ab3) were revealed. The screening of Ab3 isotypes showed the presence of IgG Ab3 and more interestingly of IgE Ab3, i.e., the same isotype as Ab1. These IgE and IgG antibodies recognized predominantly the 26-kDa Ag and were cytotoxic for schistosomula in the presence of platelets for IgE Ab3 and eosinophils for IgG Ab3. Both IgE and IgG Ab3 conferred by passive transfer protective immunity to infected rats (up to 50%). Thus the immunization with an IgE mAb led in part to the production of Ab3 of the same isotype as Ab1. In conclusion, these results suggest that the isotype selection of the antibodies of the third generation (Ab3) might be influenced by the Ab1. The respective role of the idiotope and isotype of Ab1 in isotype regulation is discussed.
Animals↗
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↗
Persistent antibody response to the HIV-1-negative regulatory factor in HIV-1-infected seronegative persons.
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Acquired Immunodeficiency Syndrome↗
Schistosoma mansoni and its intermediate host Biomphalaria glabrata express a common 39 kilodalton acidic protein.
Two Schistosoma mansoni proteins of 43 and 39 kDa (Sm43 and Sm39) were shown to react with rabbit antibodies produced against Biomphalaria glabrata proteins. Two-dimensional gel electrophoresis of miracidial proteins indicated that Sm43 and Sm39 were acidic proteins (pI 4.8 and 4.9 respectively) and were in vitro translated from miracidial messenger RNA in the same molecular forms. Sm43 and Sm39 were expressed by all parasite stages of S. mansoni. Using anti-Sm43 and anti-Sm39 mouse sera, we demonstrated that both parasite proteins were antigenically related and cross-reacted with a unique 39 kDa (pI 4.9) protein from B. glabrata (Bg39). Cross-reactive components were found in fresh water and land snails but not in vertebrate tissues, suggesting that the 39 kDa protein was specific for invertebrates.
Animals↗
IgE and inflammatory cells.
Extensive studies initiated in parasitic disease models have unequivocally established that IgE antibodies can directly interact with mononuclear phagocytes, eosinophils and platelets through specific surface receptors now identified as Fc epsilon RII. Genes coding for B cell and more recently eosinophil IgE receptors have been cloned. Studies on molecular structure indicate a close homology between Fc epsilon RII on inflammatory cells and on B cells but indications are emerging of some degree of heterogeneity among the second class of receptors for IgE. Recent studies performed in parallel on eosinophils indicate that their IgE receptors contain a sequence commonly involved in the primary structure of adhesion proteins. Interaction between antigen and cytophilically bound IgE antibodies results in the triggering of cell effector function and the release of a variety of pro-inflammatory or cytocidal mediators. Among others, one eosinophil granule protein (eosinophil peroxidase) is preferentially released by anaphylactic isotype-dependent stimuli. The main expression of IgE-dependent platelet activation appears related to the production of oxygen-derived free radicals (detected by chemoluminescence and electron magnetic resonance) together with their cytocidal properties. Taken together these findings confirm our current view that IgE receptors on inflammatory cells play a major role in the expression of cell effector function, both in defence mechanisms against several parasites and in allergic reactions.
Animals↗
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↗
Schistosoma mansoni-specific rat T cell clones. II. Different effects of adult worm-specific T cell clones in immunocompetent and nude infected rats.
The in vivo functional activities of two highly proliferating helper rat T cell clones (E23 and G5) specific for the excretory-secretory antigens of Schistosoma mansoni adult worms were investigated. When injected into infected immunocompetent rats, both clones increased the antibody response against the 30-40-kDa schistosomulum surface antigens, but failed to induce an immune protection. In contrast, when the same clones were injected into infected nude rats, a high degree of protection was obtained. In this latter case the absence of detectable specific antibody response, whether of IgE or IgG isotype, suggested that parasites were destroyed by an antibody-independent mechanism, i.e. macrophages activation by lymphokines. Indeed supernatants obtained from T cell clones specifically restimulated with schistosome antigens expressed a macrophage activated activity similar to interferon-gamma. Following incubation with these supernatants or with the active fractions, macrophages exhibited a significant schistosomulicidal activity and both clones were shown to transfer an antigen-specific delayed-type hypersensitivity reaction to normal rats. Taken together these results demonstrate that, depending on the immune status of the host, antigen-specific T cell clones can function differently and consequently that one function associated with one type of lymphokine could be favored.
Animals↗
Total and specific IgE in serum and cerebrospinal fluid of rats and guinea pigs infected with Angiostrongylus cantonensis.
The total and specific IgE response to Angiostrongylus cantonensis infection was evaluated according to host permissiveness. Total IgE levels measured by a double antibody radioimmunoassay (RIA) increased slowly in the permissive host (the rat), reaching a maximum between 4 and 8 weeks after infection. This maximum was earlier but significantly lower in the non-permissive host (the guinea pig). IgE antibodies specific for adult worms or L1 or L3 larvae of A. cantonensis were measured by a radioallergosorbent test (RAST). In the case of adult worms and L1 antigens, specific IgE antibody levels showed large variations in relation to the duration of infection in rats. In contrast to total IgE levels, the specific IgE response to L3 larvae was lower in rats than in guinea pigs in both the serum and cerebrospinal fluid (CSF). These results suggest variations in the total vs specific IgE response according to host permissiveness or non-permissiveness to A. cantonensis infection. These results are discussed in the context of the possible participation of IgE antibodies in immune defence.
Angiostrongylus↗
IgE and immune defense mechanism.
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Antigens, Differentiation, B-Lymphocyte↗