Nature Medicine
1, 1162 - 1166 (1995)
doi:10.1038/nm1195-1162
Gene transfer through the blood−nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritisRainer Kramer1, *, Yiping Zhang1, *, Jochen Gehrmann2, Ralf Gold1, Hans Thoenen1
& Hartmut Wekerle3
1Max-Planck-Institute for Psychiatry, D−821S2 Martinsried, Germany
2Department of Pathology, University Hospital, CH−8091 Zurich, Switzerland
*The first two authors contributed equally to the work described in this paper. This work was supported by a grant from the Volkswagen Foundation to H.W. and Y.Z., and a scholarship from the Deutsche Forschungs-gemeinschaft to R.G.
3Correspondence should be addressed to H.W. 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.
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