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