Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis

Nat Med. 1996 Feb;2(2):183-9. doi: 10.1038/nm0296-183.

Abstract

The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • Cell Separation
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Humans
  • Immunotoxins / administration & dosage*
  • Myelin Basic Protein / immunology*
  • Rats
  • Rats, Inbred Lew
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor*
  • Ricin / administration & dosage*
  • T-Lymphocyte Subsets / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*

Substances

  • Immunotoxins
  • Myelin Basic Protein
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • TNFRSF4 protein, human
  • Tnfrsf4 protein, rat
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Ricin