title: Autoimmunity following neonatal tolerance to alloantigens: role of donor I-A and I-E molecules.
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.
authors.affiliation: World Health Organization-Immunology Research and Training Center, Department of Pathology, CMU, Geneva, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Kramar
authors.forename: S
authors.initials: S
authors.lastname: Schurmans
authors.forename: M
authors.initials: M
authors.lastname: Berney
authors.forename: S
authors.initials: S
authors.lastname: Izui
authors.forename: G
authors.initials: G
authors.lastname: del Giudice
authors.forename: P H
authors.initials: PH
authors.lastname: Lambert
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D017951:Antigen Presentation; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005802:Genes, MHC Class II; D005921:Glomerulonephritis / Q000209:etiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006824:Hybridization, Genetic; D006942:Hypergammaglobulinemia / Q000209:etiology; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D015848:Interleukin-5; D007519:Isoantigens; D007371:Interferon-gamma