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Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells

Merino, Jesus
Schurmans, Stephane
Duchosal, M. A.
Published in Journal of Immunology. 1989, vol. 143, no. 7, p. 2202-2208
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.
Keywords AnimalsAnimals, Newborn/immunologyAntibodies, Antinuclear/analysisAutoimmune Diseases/etiology/ immunologyB-Lymphocytes/ immunologyCD4-Positive T-Lymphocytes/ immunology/transplantationCrosses, GeneticDNA, Single-Stranded/immunologyFemaleImmune ToleranceImmunoglobulin Allotypes/analysisImmunoglobulin Isotypes/analysisIsoantigens/ immunologyLymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, NudeSyndrome
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Other version: http://www.jimmunol.org/cgi/reprint/143/7/2202.pdf
PMID: 2570803
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