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T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice

BACKGROUND: Immunization against amyloid-β (Aβ), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated Aβ in transgenic mice. In a clinical tri...

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Autores principales: Meyer-Luehmann, Melanie, Mora, J Rodrigo, Mielke, Matthew, Spires-Jones, Tara L, de Calignon, Alix, von Andrian, Ulrich H, Hyman, Bradley T
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068114/
https://www.ncbi.nlm.nih.gov/pubmed/21388539
http://dx.doi.org/10.1186/1750-1326-6-22
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author Meyer-Luehmann, Melanie
Mora, J Rodrigo
Mielke, Matthew
Spires-Jones, Tara L
de Calignon, Alix
von Andrian, Ulrich H
Hyman, Bradley T
author_facet Meyer-Luehmann, Melanie
Mora, J Rodrigo
Mielke, Matthew
Spires-Jones, Tara L
de Calignon, Alix
von Andrian, Ulrich H
Hyman, Bradley T
author_sort Meyer-Luehmann, Melanie
collection PubMed
description BACKGROUND: Immunization against amyloid-β (Aβ), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated Aβ in transgenic mice. In a clinical trial of Aβ immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization. RESULTS: To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti Aβ IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas. CONCLUSIONS: Our results indicate that vaccination can lead to Aβ and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.
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spelling pubmed-30681142011-03-31 T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice Meyer-Luehmann, Melanie Mora, J Rodrigo Mielke, Matthew Spires-Jones, Tara L de Calignon, Alix von Andrian, Ulrich H Hyman, Bradley T Mol Neurodegener Research Article BACKGROUND: Immunization against amyloid-β (Aβ), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated Aβ in transgenic mice. In a clinical trial of Aβ immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization. RESULTS: To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti Aβ IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas. CONCLUSIONS: Our results indicate that vaccination can lead to Aβ and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity. BioMed Central 2011-03-09 /pmc/articles/PMC3068114/ /pubmed/21388539 http://dx.doi.org/10.1186/1750-1326-6-22 Text en Copyright ©2011 Meyer-Luehmann et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Meyer-Luehmann, Melanie
Mora, J Rodrigo
Mielke, Matthew
Spires-Jones, Tara L
de Calignon, Alix
von Andrian, Ulrich H
Hyman, Bradley T
T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice
title T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice
title_full T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice
title_fullStr T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice
title_full_unstemmed T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice
title_short T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice
title_sort t cell mediated cerebral hemorrhages and microhemorrhages during passive aβ immunization in appps1 transgenic mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068114/
https://www.ncbi.nlm.nih.gov/pubmed/21388539
http://dx.doi.org/10.1186/1750-1326-6-22
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