Scientific article

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

Published inJournal of autoimmunity, vol. 8, no. 2, p. 177-192
Publication date1995

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.

  • Animals
  • Animals, Newborn/ immunology
  • Antibodies, Monoclonal/immunology
  • Antibody Specificity
  • Antigen Presentation
  • Autoantibodies/biosynthesis/immunology
  • Autoimmune Diseases/ immunology/pathology
  • B-Lymphocytes/immunology
  • Disease Models, Animal
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, MHC Class II
  • Glomerulonephritis/etiology
  • Histocompatibility Antigens Class II/genetics/ immunology
  • Hybridization, Genetic
  • Hypergammaglobulinemia/etiology
  • Immune Tolerance
  • Immunotherapy, Adoptive/adverse effects
  • Interferon-gamma/biosynthesis
  • Interleukin-5/biosynthesis
  • Isoantigens/administration & dosage/ immunology
  • Lupus Erythematosus, Systemic/ immunology
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Mice
  • Mice, Inbred C57BL
  • Spleen/cytology
  • T-Lymphocyte Subsets/immunology
  • T-Lymphocytes, Cytotoxic/immunology
  • Th2 Cells/immunology
Citation (ISO format)
KRAMAR, G. et al. Autoimmunity following neonatal tolerance to alloantigens: role of donor I-A and I-E molecules. In: Journal of autoimmunity, 1995, vol. 8, n° 2, p. 177–192. doi: 10.1006/jaut.1995.0014
Updates (1)
ISSN of the journal0896-8411

Technical informations

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