Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss.
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Authors
Kreutzfeldt, MarioBergthaler, Andreas
Fernandez, Marylise
Brück, Wolfgang
Steinbach, Karin
Vorm, Mariann
Coras, Roland
Blümcke, Ingmar
Bonilla, Weldy V
Fleige, Anne
Forman, Ruth
Müller, Werner
Becher, Burkhard
Misgeld, Thomas
Kerschensteiner, Martin
Pinschewer, Daniel D
Merkler, Doron
Issue Date
2013-09-23
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Show full item recordAbstract
Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8(+) T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-γ (IFN-γ) and neuronal IFN-γ signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-γ blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-γ signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease.Citation
Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss. 2013, 210 (10):2087-103 J. Exp. Med.Affiliation
Department of Pathology and Immunology and 2 World Health Organization Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva, Switzerland.PubMed ID
23999498Type
ArticleLanguage
enISSN
1540-9538ae974a485f413a2113503eed53cd6c53
10.1084/jem.20122143
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