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1. Atopic sensitization in the first year of life

Author

Markus J. Ege, Erika von Mutius, Juha Pekkanen, Marjut Roponen, Roger Lauener, Jean-Charles Dalphin, Caroline Roduit, Juliane Weber, Josef Riedler, Charlotte Braun-Fahrländer, Martin Depner, Jon Genuneit, Petra Ina Pfefferle, Maija-Riitta Hirvonen, Susanne Krauss-Etschmann, Vincent Kaulek, Institute of Epidemiology, Universität Ulm, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, Universität Ulm - Ulm University [Ulm, Allemagne], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Zurich, and Depner, Martin

Subjects
Male, Rural Population, Pediatrics, MESH: Maternal-Fetal Exchange, First year of life, medicine.disease_cause, Immunoglobulin E, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, atopic sensitization, early life, environmental exposures, 0302 clinical medicine, Allergen, MESH: Pregnancy, MESH: Rural Population, Pregnancy, Surveys and Questionnaires, Immunology and Allergy, MESH : Female, Maternal-Fetal Exchange, Sensitization, MESH : Allergens, 2. Zero hunger, 0303 health sciences, biology, MESH: Immunoglobulin E, MESH : Questionnaires, MESH : Infant, Fetal Blood, MESH: Infant, 3. Good health, Europe, medicine.anatomical_structure, Cord blood, 2723 Immunology and Allergy, Female, medicine.medical_specialty, MESH: Allergens, MESH: Hypersensitivity, MESH : Male, Immunology, MESH: Environmental Exposure, MESH : Europe, Atopic sensitization, 610 Medicine & health, MESH : Immunoglobulin E, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, medicine, Hypersensitivity, Humans, MESH: Fetal Blood, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH : Fetal Blood, 2403 Immunology, MESH: Humans, MESH : Hypersensitivity, business.industry, MESH: Questionnaires, MESH : Humans, Infant, MESH : Maternal-Fetal Exchange, Odds ratio, Environmental Exposure, Allergens, medicine.disease, MESH: Male, MESH : Rural Population, MESH : Pregnancy, 030228 respiratory system, 10036 Medical Clinic, biology.protein, MESH: Europe, business, MESH: Female, MESH : Environmental Exposure
Abstract

International audience; BACKGROUND: There is conflicting evidence on whether allergen-specific memory is primed prenatally, whether this priming affects persistent immunologic effects, and whether it is modulated by the first environmental exposures in infancy. OBJECTIVE: We sought to explore the course of atopic sensitization between birth and 12 months of age. METHODS: Specific IgE levels for 6 food and 13 common inhalant allergens were assessed in cord blood and 1-year blood samples in the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort including 793 children from rural regions of 5 European countries. Detailed information on children's health, nutrition, and farm-related exposures was gathered by using a pregnancy questionnaire, 2 questionnaires at 2 and 12 months of age, and a diary covering the time in between. RESULTS: Sensitization was more common at 12 months of age than at birth for almost all specificities. On an individual level, persistent sensitization to the same allergens was rare (1%), whereas transient (only at birth, 11%) and incident (only at 12 months, 34%) sensitization was seen in substantial proportions of children. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, with the strongest associations for food allergens (odds ratio [OR], 10.6; 95% CI, 6.0-18.6) and the weakest associations for seasonal allergens (OR, 1.64; 95% CI, 0.94-2.86). Associations of maternal sensitization with incident sensitization were also seen. Incident sensitization was related to distinct prenatal and postnatal environmental exposures of mother and child, such as consumption of cereals for incident sensitization to seasonal allergens (OR, 0.66; 95% CI, 0.50-0.88). CONCLUSION: IgE sensitization patterns change between birth and 12 months and are related to maternal and environmental influences.

Published
2013
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2. Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin

Author

Jean-Michel Goujon, Mathieu Boimard, Corinne Lacombe, Violaine Planté-Bordeneuve, Philip N. Hawkins, Monica Stoppini, Julie A. Vrana, Mark B. Pepys, Guy Touchard, Vittorio Bellotti, Riccardo Porcari, Thierry Maisonobe, Franck Bridoux, Sophie Valleix, Julian D. Gillmore, Ahmet Dogan, Martino Bolognesi, Jason D. Theis, Pierre Lozeron, Sofia Giorgetti, Marc Delpech, Catherine Lacroix, Stefano Ricagno, David H. Adams, Brigitte Nedelec, Palma Mangione, Laboratoire de Biochimie et Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'anatomopathologie, Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Ischémie - Reperfusion en transplatation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Male, MESH: Hydrogen-Ion Concentration, Proteome, MESH: Protein Structure, Quaternary, MESH : beta 2-Microglobulin, MESH : Diarrhea, MESH: Monitoring, Physiologic, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Genes, Dominant, 0303 health sciences, MESH: Middle Aged, biology, Amyloidosis, MESH: Infant, Newborn, Fibrillogenesis, MESH : Genes, Dominant, General Medicine, Middle Aged, MESH : Amyloidosis, Familial, Pedigree, MESH: Glass, MESH: Proteome, MESH: Diarrhea, Sjogren's Syndrome, MESH : Glass, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Protein folding, MESH: beta 2-Microglobulin, MESH : Scalp, Amyloidosis, Familial, Diarrhea, medicine.medical_specialty, Amyloid, MESH: Pedigree, MESH : Male, MESH : Proteome, MESH : Infant, Newborn, Fibril, MESH: Scalp, 03 medical and health sciences, MESH : Hydrogen-Ion Concentration, MESH : Protein Structure, Quaternary, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH: Fetal Blood, Protein Structure, Quaternary, 030304 developmental biology, MESH : Fetal Blood, MESH: Humans, Beta-2 microglobulin, business.industry, MESH : Humans, MESH : Monitoring, Physiologic, MESH: Electrodes, medicine.disease, MESH: Amyloidosis, Familial, In vitro, MESH: Male, Transthyretin, Endocrinology, MESH: Sjogren's Syndrome, MESH : Pedigree, biology.protein, MESH : Sjogren's Syndrome, beta 2-Microglobulin, business, MESH: Genes, Dominant, MESH: Female, 030217 neurology & neurosurgery, MESH : Electrodes
Abstract

International audience; We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.

Published
2012
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3. Prenatal and early-life exposures alter expression of innate immunity genes: the PASTURE cohort study

Author

Charlotte Braun-Fahrländer, S. Bitter, Juha Pekkanen, Juliane Weber, Jon Genuneit, Jean-Charles Dalphin, Remo Frei, Josef Riedler, Johanna Wohlgensinger, Caroline Roduit, Sven Michel, Maija-Riitta Hirvonen, Erika von Mutius, Marie Laure Dalphin, Roger Lauener, Marjut Roponen, Georg Loss, Michael Kabesch, Institute of Epidemiology, Universität Ulm - Ulm University [Ulm, Allemagne], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service Pédiatrie, Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, Universität Ulm, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), and Hôpital Saint-Jacques-Université de Franche-Comté ( UFC )

Subjects
Hypersensitivity, Immediate, Male, Rural Population, MESH : RNA, Messenger, MESH : Prenatal Exposure Delayed Effects, MESH : Prospective Studies, Lipopolysaccharide Receptors, Gene Expression, MESH : Agriculture, MESH : Hypersensitivity, Immediate, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, MESH: Pregnancy, MESH: Rural Population, Pregnancy, Surveys and Questionnaires, Immunology and Allergy, MESH : Female, MESH: Animals, Prospective Studies, MESH: Maternal Exposure, 2. Zero hunger, 0303 health sciences, MESH: Antigens, CD14, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Toll-Like Receptors, MESH : Questionnaires, MESH : Infant, MESH : Maternal Exposure, Agriculture, MESH : Adult, MESH : Immunity, Innate, Fetal Blood, MESH: Infant, Milk, Maternal Exposure, Prenatal Exposure Delayed Effects, MESH: Immunity, Innate, Female, MESH: Cats, MESH: Hypersensitivity, Immediate, MESH : Cats, MESH: Agriculture, MESH: Toll-Like Receptors, Adult, MESH: Gene Expression, CD14, MESH : Male, Immunology, Biology, Polymorphism, Single Nucleotide, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, Immunity, Animals, Humans, MESH: Fetal Blood, RNA, Messenger, 030304 developmental biology, MESH: RNA, Messenger, MESH : Fetal Blood, Innate immune system, MESH: Humans, MESH: Questionnaires, MESH : Humans, TLR9, Infant, MESH: Adult, TLR7, TLR8, MESH: Male, MESH: Prospective Studies, Immunity, Innate, MESH : Rural Population, MESH : Gene Expression, MESH: Milk, MESH : Pregnancy, MESH : Antigens, CD14, 030228 respiratory system, MESH : Milk, TLR6, MESH : Toll-Like Receptors, TLR4, Cats, MESH : Animals, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

International audience; BACKGROUND: There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures. OBJECTIVE: We sought to determine environmental and nutritional exposures associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child's life. METHODS: For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n= 938) and year 1 (n= 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis. RESULTS: Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers (P for multifactorial multivariate ANOVA= .041), significantly so for TLR7 (adjusted geometric means ratio [aGMR], 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found. CONCLUSION: Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life.

Published
2012
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4. Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial

Author

Vassilis, Tsatsaris, Catherine, Capitant, Thomas, Schmitz, Corine, Chazallon, Sophie, Bulifon, Didier, Riethmuller, Olivier, Picone, Patrice, Poulain, Fanny, Lewin, Fabrice, Lainé, Evelyne, Jacqz-Aigrain, Jean-Pierre, Aboulker, Odile, Launay, Elisabeth, Moreau, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie-obstétrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Fer et Métabolismes, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CIC - Biotherapie - AP-HP (cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM), French National Institute of Health and Medical Research, programme de recherches H1N1 Aviesan, Institut de Microbiologie et des Maladies Infectieuses, Inserm C09-33 PREFLUVAC (Immunogenicity and Safety of an Inactivated Nonadjuvanted A[H1N1v] Influenza Vaccine in Pregnant Women) Study Group., Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Biologie du développement et reproduction ( BDR ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH : Prospective Studies, MESH: Maternal-Fetal Exchange, MESH : Pregnancy Trimester, Third, MESH : Pregnancy Trimester, Second, medicine.disease_cause, Antibodies, Viral, MESH: Influenza Vaccines, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, MESH: Pregnancy, Pregnancy, Influenza A virus, Medicine, MESH : Female, MESH : Influenza, Human, 030212 general & internal medicine, Prospective Studies, Pregnancy Complications, Infectious, Maternal-Fetal Exchange, 030219 obstetrics & reproductive medicine, MESH: Middle Aged, biology, MESH: Influenza, Human, MESH: Neutralization Tests, MESH: Infant, Newborn, Antibody titer, General Medicine, MESH : Adult, Middle Aged, Fetal Blood, MESH : Influenza A Virus, H1N1 Subtype, 3. Good health, Vaccination, Titer, Influenza Vaccines, MESH: Young Adult, MESH: Hemagglutination Inhibition Tests, Pregnancy Trimester, Second, MESH: Pregnancy Trimester, Second, MESH: Pregnancy Trimester, Third, Gestation, Female, Antibody, MESH : Antibodies, Viral, Adult, medicine.medical_specialty, Adolescent, Pregnancy Trimester, Third, MESH : Young Adult, MESH : Neutralization Tests, MESH : Infant, Newborn, MESH: Influenza A Virus, H1N1 Subtype, 03 medical and health sciences, Young Adult, Neutralization Tests, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Influenza, Human, Internal Medicine, Humans, MESH : Middle Aged, MESH: Pregnancy Complications, Infectious, MESH: Fetal Blood, Seroconversion, MESH : Fetal Blood, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, Infant, Newborn, MESH : Maternal-Fetal Exchange, MESH: Adult, Hemagglutination Inhibition Tests, medicine.disease, MESH : Hemagglutination Inhibition Tests, MESH : Influenza Vaccines, MESH: Prospective Studies, MESH : Pregnancy, MESH : Pregnancy Complications, Infectious, Immunology, biology.protein, business, MESH: Female, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BACKGROUND: Pregnant women and infants who get influenza are at increased risk for severe illness. OBJECTIVE: To evaluate the immunogenicity and transplacental antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during pregnancy. DESIGN: Prospective, multicenter, single-group clinical trial. (ClinicalTrials.gov registration number: NCT01024400) SETTING: Five level-3 perinatal centers in France. PATIENTS: 107 pregnant women between 22(0/7) and 32(0/7) weeks of gestation. INTERVENTION: An intramuscular dose of a nonadjuvanted H1N1 vaccine that contained 15 mcg of hemagglutinin. MEASUREMENTS: Proportion of women with an influenza antibody titer of 1:40 or greater at days 21 and 42 after vaccination, delivery, and 3 months after delivery. Seroconversion rate, fold increase in the geometric mean titer 21 days after vaccination, and proportion of neonates with an antibody titer of 1:40 or greater at birth were also assessed. RESULTS: At baseline, 19% of the women had an antibody titer of 1:40 or greater. At day 21, 98% of the women had an antibody titer of 1:40 or greater, the seroconversion rate was 93%, and the fold increase in geometric mean titer was 67.4. At day 42, delivery, and 3 months after delivery, 98%, 92%, and 90% of the women, respectively, had an antibody titer of 1:40 or greater. Ninety-five percent of the cord serum samples obtained from 88 neonates showed an antibody titer of 1:40 or greater. The median neonate-mother antibody titer ratio was 1.4. LIMITATIONS: Only healthy pregnant women were selected. Data on hemagglutination inhibition antibody titers of infants were reported only at birth. CONCLUSION: A single dose of a nonadjuvanted influenza A(H1N1) vaccine with 15 mcg of hemagglutinin triggered a strong immune response in pregnant women and a high rate of neonatal seroprotection. PRIMARY FUNDING SOURCE: French National Institute of Health and Medical Research.

Published
2011
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5. Human cord blood-derived hematopoietic and neural-like stem/progenitor cells are attracted by the neurotransmitter GABA

Author

Frédéric Deschaseaux, Pierre Tiberghien, Norbert Balon, Vincent Zangiacomi, Stéphane Maddens, Claudine Versaux-Botteri, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Saas, Philippe

Subjects
MESH: Chemotaxis, MESH : Cell Line, Baclofen, MESH: Neurons, Fluorescent Antibody Technique, Gene Expression, MESH: Flow Cytometry, MESH: gamma-Aminobutyric Acid, MESH: GABA Antagonists, MESH: Hematopoietic Stem Cells, GABA Antagonists, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, AC133 Antigen, MESH: Receptors, GABA-B, MESH: Antigens, CD, MESH: Fluorescent Antibody Technique, MESH: Receptors, GABA-A, Cells, Cultured, gamma-Aminobutyric Acid, Neurons, MESH : GABA Antagonists, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH: Peptides, MESH : Peptides, Chemotaxis, Stem Cells, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Bicuculline, Cell Differentiation, Hematology, Fetal Blood, Flow Cytometry, MESH : gamma-Aminobutyric Acid, 3. Good health, Cell biology, Endothelial stem cell, MESH: Baclofen, Haematopoiesis, Cord blood, MESH : Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Cell Differentiation, MESH : Colony-Forming Units Assay, Adult stem cell, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Gene Expression, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Flow Cytometry, MESH: Glycoproteins, MESH: Stem Cells, Biology, Bicuculline, MESH : Neurons, Cell Line, Colony-Forming Units Assay, 03 medical and health sciences, MESH: Bicuculline, Antigens, CD, MESH : Cells, Cultured, MESH : Antigens, CD, MESH : Baclofen, Humans, MESH: Colony-Forming Units Assay, MESH: Fetal Blood, GABA-A Receptor Antagonists, Progenitor cell, Glycoproteins, 030304 developmental biology, Interleukin 3, MESH : Fetal Blood, MESH: Humans, MESH : Hematopoietic Stem Cells, MESH : Humans, MESH : Receptors, GABA-A, MESH : Receptors, GABA-B, Cell Biology, Hematopoietic Stem Cells, Receptors, GABA-A, MESH : Glycoproteins, MESH: Cell Line, MESH : Gene Expression, MESH : Fluorescent Antibody Technique, Receptors, GABA-B, nervous system, MESH : Chemotaxis, Cell culture, Immunology, Peptides, GABA-B Receptor Antagonists, 030217 neurology & neurosurgery, Developmental Biology, Homing (hematopoietic)
Abstract

International audience; Migration of stem/progenitor cells is a crucial event for homing toward tissue where cells need to be renewed. The neurotransmitter gamma-aminobutyric acid (GABA) has been shown to have a crucial role in migration of neuronal stem/progenitor cells. Since human umbilical cord blood (HUCB) contains stem/progenitor cells able to generate either neuronal or hematopoietic cells, we evaluated the effect of GABA on this type of cells. While whole fraction of mononuclear cells expressed GABA(A) and GABA(B) receptor subunits (GABA-R), only GABA(B)R subunits were found to be expressed on immature CD133+ cells. Functional experiments revealed that both cell fractions of HUCB were attracted by a gradient of GABA concentration and furthermore were blocked by specific antagonists of GABA(A)R and GABA(B)R bicuculline and saclofen, respectively. Moreover, through GABA(B)R activation the migrating fraction was highly enriched by both hematopoietic progenitors and cells able to generate neuron- like cells in culture. Therefore, GABA is a potent chemoattractant of HUCB stem/progenitor cells specifically through GABA(B)R activation.

Published
2009
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6. Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE Study

Author

Charlotte Braun-Fahrländer, Susanne Krauss-Etschmann, Gisela Büchele, Bert Brunekeef, Juha Pekkanen, Anne Hyvärinen, Nicole Blümer, Erika von Mutius, Marjut Roponen, Josef Riedler, Markus J. Ege, R. Lauener, Maija-Riitta Hirvonen, Harald Renz, Petra Ina Pfefferle, Jean-Charles Dalphin, Jon Genuneit, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), European Project: 211911,EC:FP7:KBBE,FP7-KBBE-2007-1,EFRAIM(2008), Laboratoire Chrono-environnement (UMR 6249) (LCE), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), and European Project : 211911,EC:FP7:KBBE,FP7-KBBE-2007-1,EFRAIM ( 2008 )

Subjects
Hypersensitivity, Immediate, Male, MESH : Cytokines, animal diseases, MESH : Pregnancy Trimester, Third, MESH : Animals, Domestic, MESH : Agriculture, MESH : Hypersensitivity, Immediate, Lymphocyte Activation, Umbilical cord, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Nonfarm payrolls, Surveys and Questionnaires, Immunology and Allergy, MESH : Female, MESH: Animals, MESH: Maternal Exposure, MESH: Cohort Studies, 2. Zero hunger, 0303 health sciences, MESH: Cytokines, MESH: Infant, Newborn, MESH : Questionnaires, MESH : Maternal Exposure, Agriculture, MESH : Adult, Fetal Blood, Yogurt, Europe, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, MESH: Young Adult, Maternal Exposure, Cord blood, Animals, Domestic, MESH : Infant, Low Birth Weight, MESH: Pregnancy Trimester, Third, Gestation, Cytokines, Female, medicine.symptom, MESH: Hypersensitivity, Immediate, MESH: Agriculture, Adult, Offspring, MESH : Male, Pregnancy Trimester, Third, MESH : Europe, Immunology, MESH : Young Adult, MESH : Cohort Studies, MESH: Infant, Low Birth Weight, MESH : Infant, Newborn, Proinflammatory cytokine, 03 medical and health sciences, Young Adult, Animal science, medicine, Animals, Humans, MESH: Animals, Domestic, MESH: Fetal Blood, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : Fetal Blood, MESH: Humans, business.industry, MESH: Questionnaires, MESH : Humans, Infant, Newborn, MESH: Adult, MESH : Yogurt, Infant, Low Birth Weight, medicine.disease, MESH: Male, MESH: Yogurt, MESH : Leukocytes, Mononuclear, MESH : Pregnancy, Low birth weight, Leukocytes, Mononuclear, MESH : Animals, MESH: Europe, business, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030215 immunology
Abstract

International audience; BACKGROUND: Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection. OBJECTIVES: To investigate associations between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families. METHODS: Supernatants from phorbol 12-myristate 13-acetate/ionomycin-stimulated CB mononuclear cells were assessed for the production of IFN-gamma, TNF-alpha, IL-5, IL-10, and IL-12. RESULTS: Significantly higher levels of IFN-gamma and TNF-alpha in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-gamma and TNF-alpha in umbilical blood. CONCLUSION: Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth.

Published
2009
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7. Stepwise development of MAIT cells in mouse and human

Author

Claire Soudais, Ivan C. Moura, Stéphane Cherif, Hélène Laude, Emmanuel Martin, Lucia Guerri, Cécile Toly, Livine Duban, Anne Devys, Florence Tilloy, Sylvain Latour, Virginie Premel, Gabriella Vera, Olivier Lantz, Emmanuel Treiner, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U925, équipe avenir, Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Nantes], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from INSERM, Action incitative (ACI) 'physiologie integrative,' Agence Nationale pour la Recherche (ANR), and Section Médicale de l'Institut Curie. The development of the 3C10 antibody was funded in part by Innate-Pharma (Marseille, France). OL is supported by la Ligue Contre le Cancer as an 'équipe labellisée.', Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Immunité et cancer (U932), and Autard, Delphine

Subjects
Adoptive cell transfer, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Kruppel-Like Transcription Factors, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH : Child, T-Lymphocyte Subsets, MESH: Child, Cytotoxic T cell, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Biology (General), Child, Mice, Knockout, 0303 health sciences, B-Lymphocytes, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH : Immunity, Mucosal, General Neuroscience, Natural killer T cell, Fetal Blood, MESH : Mice, Transgenic, Cell biology, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Histocompatibility Antigens Class I, MESH: Kruppel-Like Transcription Factors, Antibody, General Agricultural and Biological Sciences, Research Article, Genetically modified mouse, MESH: Mice, Transgenic, QH301-705.5, Immunology, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Thymus Gland, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, MESH : B-Lymphocytes, Minor Histocompatibility Antigens, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, MESH : Thymus Gland, MESH: Fetal Blood, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity, Mucosal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : T-Lymphocytes, MESH : Fetal Blood, MESH: Humans, General Immunology and Microbiology, T-cell receptor, Histocompatibility Antigens Class I, MESH : Humans, MESH: Thymus Gland, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Gastrointestinal Tract, MESH: T-Lymphocytes, MESH: Natural Killer T-Cells, MESH: Immunity, Mucosal, biology.protein, Natural Killer T-Cells, MESH : Mice, Knockout, MESH: Gastrointestinal Tract, MESH : Animals, MESH : Gastrointestinal Tract, 030215 immunology
Abstract

Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells., Author Summary White blood cells, or lymphocytes, play an important role in defending the body from infection and disease. T lymphocytes come in many varieties with diverse functions. Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional T lymphocytes, characterized by their invariant T cell receptor (TCR)α chain and their requirement for the nonpolymorphic class Ib (MHC) molecule, MR1. MAIT cells are extremely abundant in human blood and mucosae. Contrary to mainstream T cells, their development requires B cells and commensal microbial flora. To shed light on the little-understood MAIT cells, we used new tools, including an antibody that we recently developed to detect human MAIT cells, and we were able to show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. We show that thymic selection is MR1 dependent but requires neither B cells nor the commensal flora, which are both necessary for the expansion in the periphery. In contrast with the other evolutionarily conserved invariant subset, the natural killer T (NKT) cells, we found that MAIT cells exit the thymus as “naïve” cells before becoming antigen-experienced memory cells and expanding in number to represent a significant 1%–4% of peripheral T cells in human blood. In mice, we found that MAIT cells remain naïve and do not expand substantially. We conclude that MAIT cell development follows a unique scheme, where, unlike NKT cells, MAIT cell selection and expansion are uncoupled events that are mediated by distinct cell types in different compartments., Mucosal-associated invariant T cells, the most abundant invariant T cell subset in humans, arise via a distinct developmental pathway that represents a hybrid of that seen for NKT and γδ T cells, two other unconventional T cell subsets.

Published
2009
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8. Cord blood allergen-specific IgE is associated with reduced IFN-gamma production by cord blood cells: the Protection against Allergy-Study in Rural Environments (PASTURE) Study

Author

Pfefferle , Petra Ina, Sel , Serdar, Ege , Markus Johannes, Büchele , Gisela, Blümer , Nicole, Krauss-Etschmann , Susanne, Herzum , Ileana, Albers , Christoph E, Lauener , Roger P, Roponen , Marjut, Hirvonen , Maija-Riitta, Vuitton , Dominique A, Riedler , Josef, Brunekreef , Bert, Dalphin , Jean-Charles, Braun-Fahrländer , Charlotte, Pekkanen , Juha, Von Mutius , Erika, Renz , Harald, Renseigné , Non, WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, SERF Unit, Université de Franche-Comté ( UFC ), Division of Occupational and Environmental Health, Institute for Risk Assessment ( IRAS ), Utrecht University [Utrecht], Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), European Project : 211911,EC:FP7:KBBE,FP7-KBBE-2007-1,EFRAIM ( 2008 ), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Occupational and Environmental Health, Institute for Risk Assessment (IRAS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), European Project: 211911,EC:FP7:KBBE,FP7-KBBE-2007-1,EFRAIM(2008), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), and Laboratoire Chrono-environnement (UMR 6249) (LCE)

Subjects
Male, Rural Population, Allergy, MESH : Prospective Studies, medicine.disease_cause, Immunoglobulin E, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Allergic sensitization, MESH: Pregnancy, 0302 clinical medicine, Allergen, MESH: Rural Population, Antibody Specificity, Pregnancy, Immunology and Allergy, MESH : Female, Prospective Studies, Sensitization, MESH : Allergens, MESH : Antibody Specificity, 0303 health sciences, biology, MESH: Immunoglobulin E, MESH: Infant, Newborn, MESH : Adult, Fetal Blood, 3. Good health, Europe, medicine.anatomical_structure, Cord blood, Female, Antibody, Food Hypersensitivity, Adult, MESH : Food Hypersensitivity, MESH: Allergens, MESH : Interleukin-5, MESH: Interferon-gamma, MESH : Male, Immunology, MESH : Europe, MESH : Infant, Newborn, MESH : Immunoglobulin E, 03 medical and health sciences, Interferon-gamma, Immune system, medicine, Humans, MESH: Fetal Blood, MESH: Antibody Specificity, MESH : Interferon-gamma, 030304 developmental biology, MESH : Fetal Blood, MESH: Humans, business.industry, MESH : Humans, Infant, Newborn, MESH: Adult, Allergens, MESH: Interleukin-5, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH : Rural Population, MESH : Pregnancy, 030228 respiratory system, MESH: Food Hypersensitivity, biology.protein, MESH: Europe, Interleukin-5, business, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

International audience; BACKGROUND: It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants. OBJECTIVE: To investigate the relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences. METHODS: As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-gamma, IL-10, and TNF-alpha. RESULTS: Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-gamma production, but not with IL-5 and IL-10. CONCLUSION: Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-gamma production.

Published
2008
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9. Cord blood-derived neurons are originated from CD133+/CD34 stem/progenitor cells in a cell-to-cell contact dependent manner

Author

Valérie Lapierre, Norbert Balon, Frédéric Deschaseaux, Claudine Versaux-Botteri, Vincent Zangiacomi, Remy Schlichter, Pierre Tiberghien, Stéphane Maddens, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) ( NEURO ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Institut des Neurosciences Cellulaires et Intégratives ( INCI ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), and Saas, Philippe

Subjects
MESH : Cell Line, Cellular differentiation, CD34, MESH: Neurons, Antigens, CD34, Cell Communication, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, AC133 Antigen, MESH: Antigens, CD, Neurons, 0303 health sciences, MESH: Peptides, MESH : Peptides, Stem Cells, Cell Differentiation, Hematology, Fetal Blood, 3. Good health, Cell biology, Endothelial stem cell, medicine.anatomical_structure, Cord blood, MESH : Antigens, CD34, MESH : Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, MESH : Cell Differentiation, Adult stem cell, Subcellular Fractions, MESH: Cell Differentiation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Cell Communication, MESH: Glycoproteins, MESH: Stem Cells, Biology, MESH : Subcellular Fractions, MESH : Neurons, Cell Line, 03 medical and health sciences, Antigens, CD, MESH: Cell Communication, medicine, MESH : Antigens, CD, Humans, MESH: Fetal Blood, Progenitor cell, 030304 developmental biology, Glycoproteins, MESH : Fetal Blood, MESH: Humans, MESH : Humans, Cell Biology, MESH: Antigens, CD34, MESH : Glycoproteins, MESH: Cell Line, nervous system, MESH: Subcellular Fractions, Immunology, Neuron, Peptides, 030217 neurology & neurosurgery, Developmental Biology
Abstract

International audience; Previous studies described that neurons could be generated in vitro from human umbilical cord blood cells. However, there are few data concerning their origin. Notably, cells generating neurons are not well characterized. The present study deals with the origin of cord blood cells generating neurons and mechanisms allowing the neuronal differentiation. We studied neuronal markers of both total fractions of cord blood and stem/progenitor cord blood cells before and after selections and cultures. We also compared neuronal commitment of cord blood cells to that observed for the neuronal cell line SK-N-BE(2). Before cultures, neuronal markers are found within the total fraction of cord blood cells. In CD133+ stem/progenitor cell fraction only immature neuronal markers are detected. However, CD133+ cells are unable to give rise to neurons in cultures, whereas this is achieved when total fraction of cord blood cells is used. In fact, mature functional neurons can be generated from CD133+ cells only in cell-to-cell close contact with either CD133- fraction or a neurogenic epithelium. Furthermore, since CD133+ fraction is heterogenous, we used several selections to precisely identify the phenotype of cord blood-derived neuronal stem/progenitor cells. Results reveal that only CD34- cells from CD133+ fraction possess neuronal potential. These data show the phenotype of cord blood neuronal stem/progenitor cells and the crucial role of direct cell-to-cell contact to achieve their commitment. Identifying the neuron supporting factors may be beneficial to the use of cord blood neuronal stem/progenitor cells for regenerative medicine.

Published
2008
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10. Prenatal exposure to a farm environment modifies atopic sensitization at birth

Author

Ege , Markus Johannes, Herzum , Ileana, Büchele , Gisela, Krauss-Etschmann , Susanne, Lauener , Roger P, Roponen , Marjut, Hyvärinen , Anne, Vuitton , Dominique A, Riedler , Josef, Brunekreef , Bert, Dalphin , Jean-Charles, Braun-Fahrländer , Charlotte, Pekkanen , Juha, Renz , Harald, Von Mutius , Erika, Renseigné , Non, WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, SERF Unit, Université de Franche-Comté ( UFC ), Division of Occupational and Environmental Health, Institute for Risk Assessment ( IRAS ), Utrecht University [Utrecht], Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Occupational and Environmental Health, Institute for Risk Assessment (IRAS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), University of Zurich, and Ege, M J

Subjects
Hypersensitivity, Immediate, Male, Allergy, MESH : Prospective Studies, MESH: Logistic Models, MESH : Animals, Domestic, Immunoglobulin E, MESH : Agriculture, MESH : Hypersensitivity, Immediate, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Atopy, Cohort Studies, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Surveys and Questionnaires, Immunology and Allergy, MESH: Animals, MESH : Female, Prospective Studies, MESH: Maternal Exposure, MESH: Cohort Studies, Sensitization, MESH : Allergens, 2. Zero hunger, 0303 health sciences, biology, MESH: Immunoglobulin E, MESH: Infant, Newborn, MESH : Questionnaires, Agriculture, MESH : Maternal Exposure, Environmental exposure, Fetal Blood, Europe, medicine.anatomical_structure, Maternal Exposure, Cord blood, Animals, Domestic, 2723 Immunology and Allergy, Female, MESH: Hypersensitivity, Immediate, MESH: Agriculture, MESH: Allergens, MESH : Male, Immunology, MESH: Environmental Exposure, MESH : Europe, MESH : Cohort Studies, 610 Medicine & health, Context (language use), MESH : Infant, Newborn, MESH : Immunoglobulin E, 03 medical and health sciences, medicine, Animals, Humans, MESH: Animals, Domestic, MESH: Fetal Blood, 030304 developmental biology, MESH : Fetal Blood, 2403 Immunology, MESH: Humans, business.industry, MESH: Questionnaires, MESH : Humans, Infant, Newborn, Environmental Exposure, Allergens, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH : Pregnancy, Logistic Models, 10036 Medical Clinic, biology.protein, MESH: Europe, MESH : Animals, business, MESH: Female, MESH : Environmental Exposure, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030215 immunology, MESH : Logistic Models
Abstract

International audience; BACKGROUND: Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age. OBJECTIVE: We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort. METHODS: Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers. RESULTS: Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood. CONCLUSIONS: Maternal exposure during pregnancy influences atopic sensitization patterns in cord blood. The (microbial) context of allergen contact possibly modifies the risk of atopic sensitization.

Published
2008
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