Treatment and prevention of experimental autoimmune neuritis with superagonistic CD28-specific monoclonal antibodies

J Neuroimmunol. 2003 Jul;140(1-2):143-52. doi: 10.1016/s0165-5728(03)00182-6.

Abstract

Two distinct CD28-specific mAb were used in treatment of active or adoptive transfer (AT)-experimental autoimmune neuritis (EAN): "superagonistic" JJ316 activates T cells without T cell receptor (TCR) occupancy, and conventional JJ319 activates T cells only in the presence of TCR-stimulation. Treatment with JJ316 during induction phase of active and adoptive-transfer experimental autoimmune encephalomyelitis (AT-EAN) dramatically reduced disease severity and improved nerve function as revealed by electrophysiology. JJ316 given 1 week before immunization had a preventive effect. By immunohistology, JJ316 markedly reduced TC infiltration of the sciatic nerve in active and AT-EAN. JJ319 was less effective. Ex vivo, JJ316 therapy reduced P2-specific proliferation and interferon-gamma (IFN-gamma) production of lymph node cells. We demonstrate preventive and therapeutic effects of a "superagonistic" mAb-mediated, TCR-independent CD28 stimulation in EAN, possibly with implications for therapy of autoimmune-inflammatory disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / therapeutic use*
  • CD28 Antigens / immunology*
  • Cell Division / immunology
  • Cell Line
  • Cell Movement / immunology
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Immunity, Active
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Injections, Intraperitoneal
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation / immunology
  • Myelin P2 Protein / immunology
  • Neuritis, Autoimmune, Experimental / immunology*
  • Neuritis, Autoimmune, Experimental / pathology
  • Neuritis, Autoimmune, Experimental / physiopathology
  • Neuritis, Autoimmune, Experimental / prevention & control*
  • Peptide Fragments / immunology
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve / immunology
  • Sciatic Nerve / physiopathology
  • Severity of Illness Index
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • T-Lymphocytes / transplantation

Substances

  • Antibodies, Monoclonal
  • CD28 Antigens
  • Epitopes, T-Lymphocyte
  • Immunosuppressive Agents
  • Myelin P2 Protein
  • Peptide Fragments
  • Interferon-gamma