Fas/Fas ligand pathway, apoptosis, and clonal anergy involved in systemic acetylcholine receptor T cell epitope tolerance

J Immunol. 2001 Mar 1;166(5):3458-67. doi: 10.4049/jimmunol.166.5.3458.

Abstract

The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, alpha 146--162 peptide-induced tolerance in experimental myasthenia gravis were examined. CD4 cells are the prime target for alpha 146--162 peptide-induced tolerance. The expression of CD69, Fas, and B7.2 molecules on AChR-immune lymphocytes was enhanced within 4--12 h after tolerance induction. A high dose of alpha 146--162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice deficient in Fas and Fas ligand, respectively. A high dose of alpha 146--162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Further, reconstitution of IL-2 in vitro-recovered alpha 146--162 peptide tolerized T cell proliferation, IFN-gamma, and IL-10 production. The findings implicate the possible role of Fas-/Fas ligand-mediated apoptosis and the resulting clonal anergy as the mechanisms of high dose AChR alpha 146--162 peptide-induced tolerance on CD4 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Amino Acid Sequence
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Apoptosis / genetics
  • Apoptosis / immunology*
  • Autoantibodies / biosynthesis
  • B7-2 Antigen
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Clonal Anergy / genetics
  • Clonal Anergy / immunology*
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Immunologic
  • Drug Administration Schedule
  • Epitopes, T-Lymphocyte / immunology*
  • Fas Ligand Protein
  • Freund's Adjuvant / administration & dosage
  • Freund's Adjuvant / immunology
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Kinetics
  • Lectins, C-Type
  • Ligands
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocyte Activation / genetics
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Molecular Sequence Data
  • Myasthenia Gravis, Autoimmune, Experimental / genetics
  • Myasthenia Gravis, Autoimmune, Experimental / immunology
  • Myasthenia Gravis, Autoimmune, Experimental / prevention & control
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Cholinergic / administration & dosage
  • Receptors, Cholinergic / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Species Specificity
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Torpedo
  • fas Receptor / biosynthesis
  • fas Receptor / genetics
  • fas Receptor / physiology*

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Autoantibodies
  • B7-2 Antigen
  • CD69 antigen
  • Cd86 protein, mouse
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Lectins, C-Type
  • Ligands
  • Membrane Glycoproteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Cholinergic
  • fas Receptor
  • Freund's Adjuvant