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Autoimmunity following neonatal tolerance to alloantigens: role of donor I-A and I-E molecules

Kramar, G.
Schurmans, Stephane
Berney, M.
Published in Journal of Autoimmunity. 1995, vol. 8, no. 2, p. 177-192
Abstract The injection of semi-allogeneic F1 spleen cells into newborn mice of a parental strain induces a state of immune tolerance characterized by anti-donor CTL unresponsiveness and the appearance of a transient SLE-like autoimmune syndrome associating autoantibody production, hypergammaglobulinemia, splenomegaly and glomerulonephritis. Our previous experiments have demonstrated that host Th2-like CD4+ T lymphocytes activate donor F1 B cells persisting in the host to produce autoantibodies, and that this cellular interaction relies on the presence of alloMHC class II molecules on donor B cells. In order to investigate the role and the involvement of MHC alloantigens in the cellular T(host)-B(donor) interaction, newborn C57BL/6 (B6) mice were injected with F1 spleen cells differing from the host at the level of defined portions of the MHC class I (K) or class II (I-A and I-E) molecules. B6 mice injected at birth with spleen cells from different F1 strains were tolerant to each alloantigen (alloAg) tested, as assessed by specific anti-donor CTL unresponsiveness. However, the SLE-like autoimmune syndrome only developed in B6 mice injected at birth with F1 spleen cells differing at the level of MHC class II I-A or I-E molecules. Autoantibodies appeared later in B6 mice neonatally tolerized to I-E alloAg than those detected in B6 mice neonatally tolerized to I-A alloAg. These results show that the SLE-like autoimmune disease that develops concomitantly to neonatally-induced tolerance to alloAg is the consequence of cognate T host-B donor cellular interactions triggered by even minute differences in the MHC class II I-A or MHC class II I-E molecules.
Keywords AnimalsAnimals, Newborn/ immunologyAntibodies, Monoclonal/immunologyAntibody SpecificityAntigen PresentationAutoantibodies/biosynthesis/immunologyAutoimmune Diseases/ immunology/pathologyB-Lymphocytes/immunologyDisease Models, AnimalGene Rearrangement, beta-Chain T-Cell Antigen ReceptorGenes, MHC Class IIGlomerulonephritis/etiologyHistocompatibility Antigens Class II/genetics/ immunologyHybridization, GeneticHypergammaglobulinemia/etiologyImmune ToleranceImmunotherapy, Adoptive/adverse effectsInterferon-gamma/biosynthesisInterleukin-5/biosynthesisIsoantigens/administration & dosage/ immunologyLupus Erythematosus, Systemic/ immunologyLymphocyte ActivationLymphocyte CooperationMiceMice, Inbred C57BLSpleen/cytologyT-Lymphocyte Subsets/immunologyT-Lymphocytes, Cytotoxic/immunologyTh2 Cells/immunology
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PMID: 7612147
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