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Autoimmune syndrome after induction of neonatal tolerance to alloantigens: effects of in vivo treatment with anti-T cell subset monoclonal antibodies

Merino, Jesus
Schurmans, Stephane
Luzuy, S.
Published in Journal of Immunology. 1987, vol. 139, no. 5, p. 1426-1431
Abstract BALB/c (H-2d) mice rendered tolerant to h-2b alloantigens by neonatal injection of semiallogeneic (C57BL/6 X BALB/c)F1 spleen cells develop autoimmune features due to an abnormal activation of persisting F1 donor B cells. The role of T cells in this autoimmune syndrome was studied by in vivo treatment of tolerant mice with anti-L3T4(GK-1.5) or anti-Ly-2 (H-35-17.2) monoclonal antibodies. The treatment of tolerant mice from day 2 to day 21 of life with anti-L3T4 MAb completely prevented the occurrence of circulating immune complexes of anti-ssDNA anti-Sm and anti-hapten (FITC) IgG antibodies as well as the glomerular deposition of Ig that were usually seen in untreated tolerant mice. This effect persisted for at least 6 wk after stopping this treatment. When the injections of anti-L3T4 MAb were delayed until day 15 of life, a very significant decrease of the autoimmune manifestations was still observed. Treatment of tolerant mice with anti-Ly-2 MAb during the same period had no effects on the autoimmune disease as compared with untreated tolerant mice. No effects on the maintenance of tolerance vs H-2b alloantigens were observed after treatment with anti-L3T4 MAb, as followed by the decrease of CTL and CTL-p alloreactivity and by the persistence of F1 donor B cells, indicated by the presence of Ig bearing the Ighb donor allotype. These results suggest the existence of interactions between L3T4+ T cells and persisting autoreactive B cells from F1 donor origin in the development of the autoimmune syndrome after neonatal induction of transplantation tolerance.
Keywords AnimalsAnimals, Newborn/ immunologyAntibodies, Antinuclear/immunologyAntibodies, Monoclonal/ therapeutic useAntigen-Antibody Complex/immunologyAntigens, Differentiation, T-LymphocyteAntigens, Ly/immunologyAntigens, Surface/immunologyAutoantibodies/immunologyAutoantigens/immunologyAutoimmune Diseases/etiology/immunology/ therapyB-Lymphocytes/immunology/transplantationH-2 Antigens/administration & dosage/ immunologyImmune ToleranceImmunoglobulin G/immunologyKidney Glomerulus/analysisLymphocyte CooperationLymphocyte DepletionMiceMice, Inbred BALB C/immunologyMice, Inbred C57BL/immunologyRibonucleoproteins, Small NuclearSpleen/transplantationT-Lymphocytes/classification/ immunologySnRNP Core Proteins
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Other version: http://www.jimmunol.org/cgi/reprint/139/5/1426.pdf
PMID: 3114366
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