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Amelioration of experimental autoimmune encephalomyelitis with anti-OX40 ligand monoclonal antibody: a critical role for OX40 ligand in migration, but not development, of pathogenic T cells.

Abstract
OX40 (CD134) and its ligand (OX40L) have been implicated in T cell activation and migration. In this study, we examined the contribution of these molecules to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) by administering a neutralizing mAb against murine OX40L (RM134L) to proteolipid protein (139-151) peptide-induced EAE in SJL mice. Administration of RM134L effectively ameliorated the disease in both actively induced and adoptively transferred EAE models. Histological examination showed that the RM134L treatment greatly reduced mononuclear cell infiltration into the spinal cord. The RM134L treatment did not inhibit the development of pathogenic T cells, given that proliferative response and IFN-gamma production by draining lymph node cells were not reduced or rather enhanced upon restimulation with proteolipid protein (139-151) in vitro, and these cells effectively transferred EAE to naive SJL mice. Flow cytometric analyses showed that the RM134L treatment inhibited the accumulation of OX40-expressing CD4(+) T cells and the migration of adoptively transferred CD4(+) T cells in the spinal cord. Immunohistochemical staining showed that OX40L was most prominently expressed on endothelial cells in the inflamed spinal cord. These results suggest that the OX40/OX40L interaction plays a critical role for the migration of pathogenic T cells into the CNS in the pathogenesis of EAE.
AuthorsC Nohara, H Akiba, A Nakajima, A Inoue, C S Koh, H Ohshima, H Yagita, Y Mizuno, K Okumura
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 3 Pg. 2108-15 (Feb 01 2001) ISSN: 0022-1767 [Print] United States
PMID11160262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Ligands
  • Membrane Glycoproteins
  • OX40 Ligand
  • Receptors, Tumor Necrosis Factor
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors
Topics
  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal (administration & dosage)
  • CD4-Positive T-Lymphocytes (immunology, pathology, transplantation)
  • Cell Differentiation (immunology)
  • Cell Movement (immunology)
  • Encephalomyelitis, Autoimmune, Experimental (etiology, immunology, metabolism, therapy)
  • Female
  • Immunohistochemistry
  • Injections, Subcutaneous
  • Ligands
  • Lymph Nodes (immunology, pathology)
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred Strains
  • OX40 Ligand
  • Receptors, Tumor Necrosis Factor (biosynthesis, immunology, physiology)
  • Spinal Cord (immunology, metabolism, pathology)
  • T-Lymphocyte Subsets (immunology, metabolism, pathology)
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 (metabolism)
  • Tumor Necrosis Factors

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