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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

Authors
Publication Date
Keywords
  • Immune Tolerance
  • New Born
  • Autoimmunity
  • Alloantigen
  • Induction
  • Treatment
  • In Vivo
  • T-Lymphocyte
  • Cell Subpopulation
  • Monoclonal Antibody
  • Transplantation
  • Mouse
  • Human
  • Rodentia
  • Mammalia
  • Alloantigène
  • Traitement
  • Lymphocyte T
  • Sous Population Cellulaire
  • Anticorps Monoclonal
  • Souris
  • Homme
  • Vertebrata
  • Tolérance Immune
  • Nouveau Né
  • Autoimmunité
  • Life Sciences :: Biochemistry
  • Biophysics & Molecular Biology [F05]
  • Sciences Du Vivant :: Biochimie
  • Biophysique & Biologie Moléculaire [F05]
  • Life Sciences :: Genetics & Genetic Processes [F10]
  • Sciences Du Vivant :: Génétique & Processus Génétiques [F10]
Disciplines
  • Medicine

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

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