Involvement of CD70-CD27 interactions in the induction of experimental autoimmune encephalomyelitis

J Neuroimmunol. 2000 Sep 22;109(2):188-96. doi: 10.1016/s0165-5728(00)00324-6.

Abstract

CD70/CD27 are cell surface molecules belonging to the TNF/TNF-receptor families. Ligation of CD27 by its ligand CD70 is thought to be important in T cell activation and T cell-B cell interaction. However, the in vivo function of these molecules during the establishment of cell-mediated immunity remains unclear. In this study, we examined the contribution of CD70-CD27 interactions to cell-mediated immunity by investigating the effect of anti-CD70 mAb on the development of experimental autoimmune encephalomyelitis (EAE). Treatment of SJL/J mice with anti-CD70 mAb prevented EAE induced by immunization with PLP(139-151). The preventive effect of anti-CD70 mAb was not due to the inhibition of T cell priming and antibody production from B cells, or immune deviation. However, TNF-alpha production was suppressed by treatment with anti-CD70 mAb, indicating that the ameliorating effect of anti-CD70 mAb appeared, at least in part, to be mediated by the inhibition of TNF-alpha production. These results indicate that the CD70-CD27 interaction plays a pivotal role in the development of cell-mediated autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibody Specificity
  • Antigens, CD*
  • CD27 Ligand
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Female
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Ligands
  • Lymphocyte Activation / immunology
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Myelin Proteolipid Protein / immunology
  • Neutralization Tests
  • Peptide Fragments / immunology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CD27 Ligand
  • Cd70 protein, mouse
  • Immunoglobulin G
  • Immunoglobulin M
  • Ligands
  • Membrane Proteins
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factor-alpha
  • myelin proteolipid protein (139-151)
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma