Gene transfer through the blood-nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis

Nat Med. 1995 Nov;1(11):1162-6. doi: 10.1038/nm1195-1162.

Abstract

Nerve-specific autoimmune T lymphocytes were used as vehicles to deliver therapeutically useful neurotrophic factors across the endothelial blood-nerve barrier. P2 protein-reactive T-lymphocyte lines from Lewis rats were transduced with a recombinant retrovirus containing the mouse nerve growth factor (NGF) gene. The engineered T cells released high amounts of NGF dependent on antigenic stimulation in vitro. After intravenous injection, the T cells infiltrated the rat peripheral nervous system and persisted there for at least two weeks. Local release of NGF from engineered T cells was demonstrable by immunocytochemistry and by an anti-inflammatory effect on infiltrating macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Capillary Permeability
  • Cell Movement
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Immunoassay
  • Immunohistochemistry
  • In Situ Hybridization
  • Macrophages / immunology
  • Mice
  • Myelin P2 Protein / immunology*
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / pharmacology
  • Neuritis, Autoimmune, Experimental / pathology
  • Neuritis, Autoimmune, Experimental / therapy*
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve / pathology

Substances

  • Myelin P2 Protein
  • Nerve Growth Factors