-
Catherine Lemaire-Vieille,
Yannick Bailly,
Paul Erlich,
Corinne Loeuillet,
Jacques Brocard,
Anne-Marie Haeberlé,
Guy Bombarde,
Camille Rak,
Valérie Demais,
Chantal Dumestre-Pérard,
Jean Gagnon, Jean-Yves Cesbron
[show abstract]
[hide abstract]
ABSTRACT: Mutations within the central region of prion protein (PrP) have been shown to be associated with severe neurotoxic activity similar to that observed with Dpl, a PrP-like protein. To further investigate this neurotoxic effect, we generated lines of transgenic (Tg) mice expressing three different chimeric PrP-Dpl proteins. Chi1 (amino acids 1-57 of Dpl replaced by amino acids 1-125 of PrP) and Chi2 (amino acids 1-66 of Dpl replaced by amino acids 1-134 of PrP) abrogated the pathogenicity of Dpl indicating that the presence of a N-terminal domain of PrP (23-134) reduced the toxicity of Dpl, as reported. However, when the amino acids 1-24 of Dpl were replaced by amino acids 1-124 of PrP, Chi3 Tg mice, which express the chimeric protein at a very low level, start developing ataxia at the age of 5-7 weeks. This phenotype was not counteracted by a single copy of full-length-PrP(c) but rather by its overexpression, indicating the strong toxicity of the chimeric protein Chi3. Chi3 Tg mice exhibit severe cerebellar atrophy with a significant loss of granule cells. We concluded that aa25 to aa57 of Dpl, which are not present in Chi1 and Chi2 constructs, confer toxicity to the protein. We tested this possibility by using the 25-57 Dpl peptide in primary culture of mouse embryo cortical neurons and found a significant neurotoxic effect. This finding identifies a protein domain that plays a role in mediating Dpl-related toxicity.
Journal of Neuroscience 01/2013; 33(4):1391-9. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sex effect on the incubation period of variant Creutzfeldt-Jakob disease (vCJD) disease in human and ME-7 murine models was investigated. In the 167 vCJD cases reported in the United Kingdom as of January 2009, age at onset was significantly lower in female patients (by 2 years) than in male patients after stratification on birth cohort. In C57/Bl6N mice infected with ME-7 scrapie strain, incubation was shorter in female than in male mice. The incubation period increased in castrated male mice after intraperitoneal infection but not after intracerebral inoculation. In the absence of androgen receptors, the incubation period for prion disease increased after intraperitoneal inoculation. In ovariectomized or estrogen receptor alpha-defective female mice, no effect was observed on the incubation period of mouse prion disease. These results show that androgens influence the prion diseases incubation period after inoculation at a peripheral site.
The Journal of Infectious Diseases 08/2010; 202(4):648-54. · 6.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A growing number of studies have investigated the interaction between C1q and PrP, but the oligomeric form of PrP involved in this interaction remains to be determined. Aggregation of recombinant full-length murine PrP in the presence of 100 mm NaCl allowed us to isolate three different types of oligomers by size-exclusion chromatography. In contrast to PrP monomers and fibrils, these oligomers activate the classical complement pathway, the smallest species containing 8-15 PrP protomers being the most efficient. We used Thioflavine T fluorescence to monitor PrP aggregation and showed that, when added to the reaction, C1q has a cooperative effect on PrP aggregation and leads to the formation of C1q-PrP complexes. In these complexes, C1q interacts through its globular domains preferentially with the smallest oligomers, as shown by electron microscopy, and retains the ability to activate the classical complement pathway. Using two cell lines, we also provide evidence that C1q inhibits the cytotoxicity induced by the smallest PrP oligomers. The cooperative interaction between C1q and PrP could represent an early step in the disease, where it prevents elimination of the prion seed, leading to further aggregation.
Journal of Biological Chemistry 06/2010; 285(25):19267-76. · 4.77 Impact Factor
-
Evelyne Gout,
Virginie Garlatti,
David F Smith,
Monique Lacroix,
Chantal Dumestre-Pérard,
Thomas Lunardi,
Lydie Martin, Jean-Yves Cesbron,
Gérard J Arlaud,
Christine Gaboriaud,
Nicole M Thielens
[show abstract]
[hide abstract]
ABSTRACT: Ficolins are oligomeric innate immune recognition proteins consisting of a collagen-like region and a fibrinogen-like recognition domain that bind to pathogen- and apoptotic cell-associated molecular patterns. To investigate their carbohydrate binding specificities, serum-derived L-ficolin and recombinant H- and M-ficolins were fluorescently labeled, and their carbohydrate binding ability was analyzed by glycan array screening. L-ficolin preferentially recognized disulfated N-acetyllactosamine and tri- and tetrasaccharides containing terminal galactose or N-acetylglucosamine. Binding was sensitive to the position and orientation of the bond between N-acetyllactosamine and the adjacent carbohydrate. No significant binding of H-ficolin to any of the 377 glycans probed could be detected, providing further evidence for its poor lectin activity. M-ficolin bound preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage. To further investigate the structural basis of sialic acid recognition by M-ficolin, point mutants were produced in which three residues of the fibrinogen domain were replaced by their counterparts in L-ficolin. Mutations G221F and A256V inhibited binding to the 9-O-acetylated sialic acid derivatives, whereas Y271F abolished interaction with all sialic acid-containing glycans. The crystal structure of the Y271F mutant fibrinogen domain was solved, showing that the mutation does not alter the structure of the ligand binding pocket. These analyses reveal novel ficolin ligands such as sulfated N-acetyllactosamine (L-ficolin) and gangliosides (M-ficolin) and provide precise insights into the sialic acid binding specificity of M-ficolin, emphasizing the essential role of Tyr(271) in this respect.
Journal of Biological Chemistry 02/2010; 285(9):6612-22. · 4.77 Impact Factor
-
Evelyne Gout,
Virginie Garlatti,
David F. Smith,
Monique Lacroix,
Chantal Dumestre-Pérard,
Thomas Lunardi,
Lydie Martin, Jean-Yves Cesbron,
Gérard J. Arlaud,
Christine Gaboriaud,
Nicole M. Thielens
[show abstract]
[hide abstract]
ABSTRACT: Ficolins are oligomeric innate immune recognition proteins consisting of a collagen-like region and a fibrinogen-like recognition
domain that bind to pathogen- and apoptotic cell-associated molecular patterns. To investigate their carbohydrate binding
specificities, serum-derived L-ficolin and recombinant H- and M-ficolins were fluorescently labeled, and their carbohydrate
binding ability was analyzed by glycan array screening. L-ficolin preferentially recognized disulfated N-acetyllactosamine and tri- and tetrasaccharides containing terminal galactose or N-acetylglucosamine. Binding was sensitive to the position and orientation of the bond between N-acetyllactosamine and the adjacent carbohydrate. No significant binding of H-ficolin to any of the 377 glycans probed could
be detected, providing further evidence for its poor lectin activity. M-ficolin bound preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage. To
further investigate the structural basis of sialic acid recognition by M-ficolin, point mutants were produced in which three
residues of the fibrinogen domain were replaced by their counterparts in L-ficolin. Mutations G221F and A256V inhibited binding
to the 9-O-acetylated sialic acid derivatives, whereas Y271F abolished interaction with all sialic acid-containing glycans. The crystal
structure of the Y271F mutant fibrinogen domain was solved, showing that the mutation does not alter the structure of the
ligand binding pocket. These analyses reveal novel ficolin ligands such as sulfated N-acetyllactosamine (L-ficolin) and gangliosides (M-ficolin) and provide precise insights into the sialic acid binding specificity
of M-ficolin, emphasizing the essential role of Tyr271 in this respect.
Journal of Biological Chemistry 02/2010; 285(9):6612-6622. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fatal neurodegenerative prion diseases are caused by the transmissible PrP(Sc) prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. However, prion replication also occurs in lymphoid cells. To assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic C57/BL6J background, by bone marrow replacement with hematopoietic cells expressing different levels of PrP protein. Nine different types of chimeric mice were inoculated intraperitoneally either with the lymphotropic Rocky Mountain Laboratory (RML) strain or the non lymphotropic ME-7 scrapie strain, at different doses. Here, we clearly demonstrate that overexpression of PrP by the hematopoietic system, or the lack of PrP expression by the bone marrow derived cells, does not change the incubation time period of the disease, even when the mice are infected at limiting doses. We conclude that the hematopoietic compartment is more or less permissive to prion replication, both for RML and ME-7, but does not play a role in neuroinvasion.
PLoS ONE 01/2010; 5(10). · 4.09 Impact Factor
-
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 11/2009; 103(5):448. · 2.83 Impact Factor
-
Molecular Immunology 09/2009; 46(14):2837. · 2.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: L- and H-ficolins are serum oligomeric defense proteins consisting of a collagen-like region and a fibrinogen-like recognition domain that bind to pathogen- and apoptotic cell-associated molecular patterns. They share with mannan-binding lectin (MBL) the ability to associate with MBL-associated serine proteases (MASP)-1, -2, -3, and protein MAp19 and to trigger the lectin complement pathway through MASP-2 activation. Recent studies have revealed the essential role of Lys(55) in the collagenous region of MBL in the interaction with the MASPs and calreticulin (CRT). To test the possible involvement of the homologous residues Lys(57) of L-ficolin and Lys(47) of H-ficolin, point mutants of both proteins were produced in which these residues were mutated to Ala, Glu, or Arg. The resulting mutants exhibited oligomerization patterns and ligand binding properties similar to those of their wild-type counterparts. In contrast, all three mutations strongly inhibited the interaction of L- and H-ficolins with MAp19 and MASP-2 and impaired the ability of each ficolin to trigger the lectin pathway. In the case of MASP-1 and MASP-3, replacement of the target Lys residues by Ala or Glu abolished interaction, whereas the Lys to Arg mutations had only slight inhibitory effects. Likewise, binding of each ficolin to CRT was inhibited by mutation of Lys to Ala or Glu, but not to Arg. In conclusion, residues Lys(57) of L-ficolin and Lys(47) of H-ficolin are key components of the interaction with the MASPs and CRT, providing strong indication that MBL and the ficolins share homologous binding sites for both types of proteins.
The Journal of Immunology 02/2009; 182(1):456-65. · 5.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Innate immunity is the major host defense against invasive aspergillosis. To determine whether the collectin mannan-binding lectin (MBL) is involved in the initial protective immunity through complement activation against opportunistic fungal infections caused by Aspergillus, we performed in vitro studies on 29 different strains of Aspergillus conidia from five different species. Incubation of Aspergillus conidia in human normal serum leads to activation of the alternative pathway, whereas neither the classical nor the lectin pathways through C4 and C2 cleavage are activated. Complement response to conidia was investigated using a MBL-deficient serum and reconstitution experiments were conducted with MBL/MASPs complexes. We found that MBL can directly support C3 activation by a C2 bypass mechanism. Finally, a stronger activation of the alternative pathway was observed for the clinical strains isolated from patients with invasive aspergillosis, compared with the environmental strains.
The Journal of Immunology 12/2008; 181(10):7100-5. · 5.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP(C), for "cellular prion protein") into an abnormal state (PrP(Sc), for "scrapie prion protein"). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP(C). In contrast to its homologue PrP(C), Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP(Sc)-like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP(C) (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the alpha-helical monomer forms soluble beta-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy.
Biochemical and Biophysical Research Communications 02/2008; 365(3):478-83. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mice defective for C1q complement factor show enhanced resistance to peripheral prion inoculation, and previous work demonstrated a direct interaction between C1q and conformationally modified PrP. However, the nature and physiological consequences of this interaction remain uncharacterized. PrP amino acids 141-159 has been identified as a potential C1q binding site; we show, by both surface plasmon resonance (SPR) spectroscopy and ELISA, that C1q and its globular region bind to PrP mutagenized in the region of interest with comparable efficiency to that of wild-type protein. To test PrP's ability to activate complement, soluble oligomers of the PrP constructs were made. Only PrP and mutagenized PrP oligomers activate the classical complement cascade while PrP monomer and the C-terminal domain, both in oligomeric and in monomeric form, failed to induce activation. This suggests that a conformational change in PrP, which occurs both when PrP is bound to an SPR sensor chip and when it undergoes oligomerization, is requisite for PrP/C1q interaction and activation of the complement cascade. We propose that C1q may act as a natural sensor for prions, leading to activation of the classical complement cascade, which could result in local inflammation and subsequent recruitment of the immune cells that prions initially infect.
Cellular Microbiology 01/2008; 9(12):2870-9. · 5.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Experimental results evidenced the infectious potential of the dental pulp of animals infected with transmissible spongiform encephalopathies (TSE). This route of iatrogenic transmission of sporadic Creutzfeldt-Jakob disease (sCJD) may exist in humans via reused endodontic instruments if inadequate prion decontamination procedures are used.
To assess this risk, 10 critical parameters in the transmission process were identified, starting with contamination of an endodontic file during treatment of an infectious sCJD patient and ending with possible infection of a subsequent susceptible patient. It was assumed that a dose-risk response existed, with no-risk below threshold values. Plausible ranges of those parameters were obtained through literature search and expert opinions, and a sensitivity analysis was conducted. Without effective prion-deactivation procedures, the risk of being infected during endodontic treatment ranged between 3.4 and 13 per million procedures. The probability that more than one case was infected secondary to endodontic treatment of an infected sCJD patient ranged from 47% to 77% depending on the assumed quantity of infective material necessary for disease transmission. If current official recommendations on endodontic instrument decontamination were strictly followed, the risk of secondary infection would become quasi-null.
The risk of sCJD transmission through endodontic procedure compares with other health care risks of current concern such as death after liver biopsy or during general anaesthesia. These results show that single instrument use or adequate prion-decontamination procedures like those recently implemented in dental practice must be rigorously enforced.
PLoS ONE 02/2007; 2(12):e1330. · 4.09 Impact Factor
-
Evelyne Jouvin-Marche,
Valérie Attuil-Audenis,
Catherine Aude-Garcia,
Walid Rachidi,
Mark Zabel,
Valérie Podevin-Dimster,
Carole Siret,
Christoph Huber,
Marianne Martinic,
Jacqueline Riondel,
Christian L Villiers,
Alain Favier,
Philippe Naquet, Jean-Yves Cesbron,
Patrice N Marche
[show abstract]
[hide abstract]
ABSTRACT: Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.
The Journal of Immunology 04/2006; 176(6):3490-7. · 5.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation.
Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced.
The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%.
This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases.
BMC Infectious Diseases 09/2004; 4:26. · 3.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Expression of the cellular prion protein (PrP(c)) by host cells is required for prion replication and neuroinvasion in transmissible spongiform encephalopathies. As a consequence, identification of the cell types expressing PrP(c) is necessary to determine the target cells involved in the cerebral propagation of prion diseases. To identify the cells expressing PrP(c) in the mouse brain, the immunocytochemical localization of PrP(c) was investigated at the cellular and ultrastructural levels in several brain regions. In addition, we analyzed the expression pattern of a green fluorescent protein reporter gene under the control of regulatory sequences of the bovine prion protein gene in the brain of transgenic mice. By using a preembedding immunogold technique, neuronal PrP(c) was observed mainly bound to the cell surface and presynaptic sites. Dictyosomes and recycling organelles in most of the major neuron types also exhibited PrP(c) antigen. In the olfactory bulb, neocortex, putamen, hippocampus, thalamus, and cerebellum, the distribution pattern of both green fluorescent protein and PrP(c) immunoreactivity suggested that the transgenic regulatory sequences of the bovine PrP gene were sufficient to promote expression of the reporter gene in neurons that express immunodetectable endogenous PrP(c). Transgenic mice expressing PrP-GFP may thus provide attractive murine models for analyzing the transcriptional activity of the Prnp gene during prion infections as well as the anatomopathological kinetics of prion diseases.
The Journal of Comparative Neurology 06/2004; 473(2):244-69. · 3.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Incubation period of the new variant Creutzfeldt-Jakob disease (vCJD) from infection to clinical onset and the eventual impact of the disease remain major concerns. Based on i) epidemiological conceptualization of human exposure to BSE contaminated material, ii) exponentially decreasing susceptibility after 15 years of age, and iii) typical incubation period (IP) distributions for time from infection to onset, we have previously estimated mean incubation period and projected number of vCJD cases. In this paper, we investigate the robustness of these estimates with respect to i-iii using the UK's 113 vCJD cases with clinical onset before December 2000. Mean incubation period was estimated at 16.4 years (95% CI 11.4-24.8), 15.9 years (95% CI 11.4-22.0), 14.1 years (95% CI 10.4-24.2) with the log-normal, Gamma and Weibull distributions respectively. Corresponding predictions for the total size of the epidemic ranged from 183 to 304. Maximal susceptibility to infection between 1.3 and 15.9 years and decreasing by 15% per year of age thereafter yielded the best fit. The shape of the IP distribution did not affect the predictions. In summary, within a set of reasonable assumptions, mean incubation period for vCJD ranged from 15 to 20 years, and the eventual impact of vCJD was a few hundred patients.
Statistical Methods in Medical Research 07/2003; 12(3):221-33. · 2.44 Impact Factor
-
Jérôme Follet,
Catherine Lemaire-Vieille,
Françoise Blanquet-Grossard,
Valérie Podevin-Dimster,
Sylvain Lehmann,
Jean-Paul Chauvin,
Jean-Pierre Decavel,
Ruth Varea,
Jacques Grassi,
Michel Fontès, Jean-Yves Cesbron
[show abstract]
[hide abstract]
ABSTRACT: Prion infection relies on a continuous chain of PrP(c)-expressing tissues to spread from peripheral sites to the central nervous system (CNS). Direct neuroinvasion via peripheral nerves has long been considered likely. However, the speed of axonal flow is incompatible with the lengthy delay prior to the detection of PrP(Sc) in the brain. We hypothesized that Schwann cells could be the candidate implicated in this mechanism; for that, it has to express PrP(c) and to allow PrP(Sc) conversion. We investigated in vivo localization of PrP(c) in sciatic nerve samples from different strains of mice. We demonstrated that PrP(c) is mainly localized at the cell membrane of the Schwann cell. We also studied in vitro expression of PrP(c) in the Schwann cell line MSC-80 and demonstrated that it expresses PrP(c) at the same location. More specifically, we demonstrated that this glial cell line, when infected in vitro with the mouse Chandler prion strain, both produces the PrP(Sc) till after 18 passages and is able to transmit disease to mice, which then develop the typical signs of prion diseases. It is the first time that infection and replication of PrP(Sc) are shown in a peripheral glial cell line.
Journal of Virology 04/2002; 76(5):2434-9. · 5.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The expression of the cellular form of the prion protein (PrPc) gene is required for prion replication and neuroinvasion in transmissible spongiform encephalopathies. The identification
of the cell types expressing PrPc is necessary to understanding how the agent replicates and spreads from peripheral sites to the central nervous system. To
determine the nature of the cell types expressing PrPc, a green fluorescent protein reporter gene was expressed in transgenic mice under the control of 6.9 kb of the bovine PrP
gene regulatory sequences. It was shown that the bovine PrP gene is expressed as two populations of mRNA differing by alternative
splicing of one 115-bp 5′ untranslated exon in 17 different bovine tissues. The analysis of transgenic mice showed reporter
gene expression in some cells that have been identified as expressing PrP, such as cerebellar Purkinje cells, lymphocytes,
and keratinocytes. In addition, expression of green fluorescent protein was observed in the plexus of the enteric nervous
system and in a restricted subset of cells not yet clearly identified as expressing PrP: the epithelial cells of the thymic
medullary and the endothelial cells of both the mucosal capillaries of the intestine and the renal capillaries. These data
provide valuable information on the distribution of PrPc at the cellular level and argue for roles of the epithelial and endothelial cells in the spread of infection from the periphery
to the brain. Moreover, the transgenic mice described in this paper provide a model that will allow for the study of the transcriptional
activity of the PrP gene promoter in response to scrapie infection.
Proceedings of the National Academy of Sciences 05/2000; 97(10):5422-5427. · 9.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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 transfered. 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.
European Journal of Immunology 06/1991; 21(7):1763 - 1766. · 5.10 Impact Factor
