title: Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells.
abstract: The induction of transplantation tolerance to H-2b alloantigens in BALB/c (H-2d) mice by neonatal injection of (C57BL/6 x BALB/c)F1 spleen cells, produces an autoimmune lupus-like syndrome due to an activation of persisting F1 donor B cells. This syndrome is characterized by hypergammaglobulinaemia, high levels of anti-DNA antibodies, as well as by circulating immune complexes and glomerular deposits of Ig. The role of host T cells in this model was investigated by using athymic BALB/c nu/nu mice as recipients of normal (C57BL/6 x BALB.Igb)F1 spleen cells. In these "tolerized" BALB/c nu/nu mice, there was a persistence of F1 donor B cells but none of the autoimmune features were expressed, conversely to tolerized BALB/c nu/+ littermates. The injection of CD4+CD8- T lymphocytes from adult normal BALB/c mice in 3-wk-old tolerized BALB/c nu/nu mice triggered the appearance of all the autoimmune findings observed in euthymic tolerant mice. The autoantibodies were produced by persisting F1 donor B cells as shown by allotype analysis. More strikingly, a similar triggering of the autoimmune syndrome, including high titers of anti-DNA IgG antibodies and circulating immune complexes, was observed after injection of CD4+CD8- T cells from 2-wk-old tolerant BALB/c mice into "tolerized" BALB/c nu/nu mice. The anti-ssDNA antibodies were shown to bear only the Ighb allotype, indicating their exclusive origin from F1 donor B cells. These results imply that CD4+ T cells from the tolerant mice are necessary for the activation of autoreactive F1 B cells and for the development of the autoimmune syndrome occurring in this model. They also suggest that, although there is a marked depletion of H-2b-specific alloreactive CTL precursors in those neonatally tolerized mice, this state of tolerance can be associated with the persistence of H-2b-specific alloreactive CD4+ cells.
authors.affiliation: WHO Immunology Research and Training Centre, Department of Pathology, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Merino
authors.forename: S
authors.initials: S
authors.lastname: Schurmans
authors.forename: M A
authors.initials: MA
authors.lastname: Duchosal
authors.forename: S
authors.initials: S
authors.lastname: Izui
authors.forename: P H
authors.initials: PH
authors.lastname: Lambert
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000974:Antibodies, Antinuclear / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003433:Crosses, Genetic; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007126:Immunoglobulin Allotypes / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013577:Syndrome
chemical_list: D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D007126:Immunoglobulin Allotypes; D007132:Immunoglobulin Isotypes; D007519:Isoantigens