Gene transfer through the blood-nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis.
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.
Kramer
R
R
Max-Planck-Institute for Psychiatry, Martinsried, Germany.
Zhang
Y
Y
Gehrmann
J
J
Gold
R
R
Thoenen
H
H
Wekerle
H
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002199:Capillary Permeability; D002465:Cell Movement; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007118:Immunoassay; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018996:Myelin P2 Protein / Q000276:immunology*; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D009444:Neuritis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology
D018996:Myelin P2 Protein; D009414:Nerve Growth Factors