Article (Scientific journals)
Thrombocytopenia associated with the induction of neonatal tolerance to alloantigens: immunopathogenic mecanisms.
Merino, J.; Qin, H.; Schurmans, Stéphane et al.
1989In European Journal of Immunology, 19, p. 1693-1699
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Keywords :
hrombocytopenia; immunopathogenic; tolerance; induction
Abstract :
[en] BALB/c mice rendered tolerant to alloantigens by neonatal injection of semi-allogeneic (C57BL/6 x BALB/c)F1 spleen cells develop a thrombocytopenia in association with an autoimmune lupus-like syndrome. The possible mechanisms involved in the thrombocytopenia were investigated. The development of thrombocytopenia was first detected at 3 weeks of age coinciding with the start of the other autoimmune manifestations and was always related to a state of tolerance and B cell chimerism. There was a significant increase of megakaryocytes in bone marrow and spleens from thrombocytopenic tolerant mice and radiolabeled platelets from these mice were more rapidly eliminated from the bloodstream than normal platelets when injected into normal recipients. A significant correlation between the spleen weight and the decrease of the circulating platelets was observed, although some mice with severe thrombocytopenia had only a moderate spleen enlargement. Thrombocytopenia significantly correlates with the levels of platelet-associated IgG (PAIgG) but not with anti-single-stranded DNA antibodies or circulating immune complexes. Platelets from mice with high levels of PAIgG had a shorter life-span when injected into normal mice than those from mice with low or normal PAIgG. The possibility that PAIgG are partially due to antibodies reacting specifically with platelet membrane components was analyzed. First, F(ab')2 Ig fragments from tolerant mice were shown to bind to normal platelets, in contrast to F(ab')2 Ig fragments from normal mice. Second, some monoclonal antibodies produced by hybridomas derived from tolerant mice reacted in vitro with platelets and induced a transient thrombocytopenia after i.v. injection into normal mice. These data suggest that the thrombocytopenia observed in tolerant mice is the result of a peripheral hyperdestruction of platelets associated with (a) hypersplenism, (b) nonspecific fixation of immunoglobulins, probably as immune complexes and (c) with autoantibodies reacting specifically with platelets. It may represent an interesting model for human chronic idiopathic thrombocytopenia
Disciplines :
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Merino, J.;  WHO Immunology Research and Training Centre, Department of Pathology, Geneva
Qin, H.;  WHO Immunology Research and Training Centre, Department of Pathology, Geneva
Schurmans, Stéphane  ;  Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Institut de Biologie et de Médecine Moléculaire
Gretener, D.;  WHO Immunology Research and Training Centre, Department of Pathology, Geneva
Grau, G.;  WHO Immunology Research and Training Centre, Department of Pathology, Geneva
Lambert, P. H.;  WHO Immunology Research and Training Centre, Department of Pathology, Geneva
Language :
English
Title :
Thrombocytopenia associated with the induction of neonatal tolerance to alloantigens: immunopathogenic mecanisms.
Publication date :
1989
Journal title :
European Journal of Immunology
ISSN :
0014-2980
eISSN :
1521-4141
Publisher :
VCH Verlagsgesellschaft, Weinheim, Germany
Volume :
19
Pages :
1693-1699
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 January 2010

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