title: Anti-inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration.
abstract: In order to analyze a putative immunomodulatory effect of NGF in experimental autoimmune encephalomyelitis (EAE) of the Lewis rat, we transduced myelin basic protein (MBP)-specific CD4(+) T cells with a recombinant retrovirus encoding NGF. These T(MBP)NGF cells secreted high levels of NGF, along with an unaltered Th1-like cytokine pattern. Transfer studies showed that T(MBP)NGF cells were unable to mediate clinical EAE, when transferred alone, and, more important, they efficiently suppressed induction of clinical EAE by non-transduced MBP-specific T cells (T(MBP )cells). In contrast, NGF transduced ovalbumin-specific T cells, which secreted high NGF levels, did not affect EAE induction. Suppression of clinical EAE by T(MBP)NGF cells was associated with a general reduction of inflammatory CNS infiltrates, with a most pronounced decrease of the monocyte/macrophage component. Using a culture model of the endothelial blood-brain barrier (BBB), we found that NGF directly acts on blood-derived monocytes via the p75 NGF receptor, thus interfering with monocyte migration through the activated BBB endothelium. Our data establish NGF as an anti-inflammatory mediator interfering with T cell mediated autoimmune disease in the CNS. They further point to monocyte migration through blood vascular endothelium as one possible mechanism of NGF action.
authors.affiliation: Max-Planck-Institute of Neurobiology, Martinsried, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Flügel
authors.forename: K
authors.initials: K
authors.lastname: Matsumuro
authors.forename: H
authors.initials: H
authors.lastname: Neumann
authors.forename: W E
authors.initials: WE
authors.lastname: Klinkert
authors.forename: R
authors.initials: R
authors.lastname: Birnbacher
authors.forename: H
authors.initials: H
authors.lastname: Lassmann
authors.forename: U
authors.initials: U
authors.lastname: Otten
authors.forename: H
authors.initials: H
authors.lastname: Wekerle
mesh_terms: D000818:Animals; D002465:Cell Movement; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D004730:Endothelium, Vascular / Q000166:cytology*; D015316:Genetic Therapy; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D009000:Monocytes / Q000502:physiology*; D020932:Nerve Growth Factor / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D020800:Receptor, Nerve Growth Factor / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000949:Histocompatibility Antigens Class II; D020800:Receptor, Nerve Growth Factor; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor